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51. Developmental and adult expression patterns of the G-protein-coupled receptor GPR88 in the rat: Establishment of a dual nuclear-cytoplasmic localization

Author: Massart, Renaud, Mignon, Virginie, Stanic, Jennifer, Munoz-Tello, Paola, BECKER, Jérôme A.J., Kieffer, Brigitte L., Darmon, Michèle, Sokoloff, Pierre, Diaz, Jorge, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Département de Neuropsychiatrie, Centre de Recherche Pierre Fabre, PRES Sorbonne Paris Cité, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), nstitut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (INSERM/CNRS), INSERM/CNRS, Douglas Hospital Research Center, Department of Psychiatry, Faculty of Medicine, Université McGill, Pierre Fabre Research Center, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), McGill University = Université McGill [Montréal, Canada], Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Physiologie de la reproduction et des comportements [Nouzilly] ( PRC ), Institut National de la Recherche Agronomique ( INRA ) -Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre National de la Recherche Scientifique ( CNRS ), Université de Strasbourg ( UNISTRA ), Institut de Génétique et de Biologie Moléculaire et Cellulaire ( INSERM/CNRS ), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], nuclear gpcrs, [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, animal model, nucleus, G protein coupled receptor, récepteur couplé aux protéines G, psychopathology, protéine g, psychopathologie, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, neocortex, animal modèle, rat, [ SDV.OT ] Life Sciences [q-bio]/Other [q-bio.OT], development
Abstract: GPR88 is a neuronal cerebral orphan G-protein-coupled receptor (GPCR) that has been linked to various psychiatric disorders. However, no extensive description of its localization has been provided so far. Here, we investigate the spatiotemporal expression of the GPR88 in prenatal and postnatal rat tissues by using in situ hybridization and immunohistochemistry. GPR88 protein was initially detected at embryonic day 16 (E16) in the striatal primordium. From E16–E20 to adulthood, the highest expression levels of both protein and mRNA were observed in striatum, olfactory tubercle, nucleus accumbens, amygdala, and neocortex, whereas in spinal cord, pons, and medulla GPR88 expression remains discrete. We observed an intracellular redistribution of GPR88 during cortical lamination. In the cortical plate of the developing cortex, GPR88 presents a classical GPCR plasma membrane/cytoplasmic localization that shifts, on the day of birth, to nuclei of neurons progressively settling in layers V to II. This intranuclear localization remains throughout adulthood and was also detected in monkey and human cortex as well as in the amygdala and hypothalamus of rats. Apart from the central nervous system, GPR88 was transiently expressed at high levels in peripheral tissues, including adrenal cortex (E16–E21) and cochlear ganglia (E19–P3), and also at moderate levels in retina (E18–E19) and spleen (E21–P7). The description of the GPR88 anatomical expression pattern may provide precious functional insights into this novel receptor. Furthermore, the GRP88 nuclear localization suggests nonclassical GPCR modes of action of the protein that could be relevant for cortical development and psychiatric disorders.
Published: 2016
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52. Prenatal stress and early-life exposure to fluoxetine have enduring effects on anxiety and hippocampal BDNF gene expression in adult male offspring

Author: Boulle, Fabien, Pawluski, Jodi L., Homberg, Judith R., Machiels, Barbie, Kroeze, Yvet, Kumar, Neha, Steinbusch, Harry W. M., Kenis, Gunter, Van den Hove, Daniel L. A., Jonchère, Laurent, Maastricht University [Maastricht], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurophysiology Unit, GIGA Neurosciences, Université de Liège, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], University of Würzburg = Universität Würzburg, JLP was funded by a Charge de Recherche position with Fonds de la Recherche Scientifique (FRS-FNRS)., Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -École des Hautes Études en Santé Publique [EHESP] ( EHESP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université des Antilles ( UA ), Radboud university [Nijmegen], University of Wuerzburg, Universität Würzburg, Centre de Psychiatrie et Neurosciences (U894), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Promovendi MHN, Psychiatrie & Neuropsychologie, Ondersteunend personeel MHN, RS: MHeNs - R3 - Neuroscience, RS: MHeNs - R2 - Mental Health, and MUMC+: MA Niet Med Staf Psychiatrie (9)
Subjects: Male, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Gene Expression, Anxiety, SEX DIFFERENCES, Hippocampus, Rats, Sprague-Dawley, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Pregnancy, Fluoxetine, Animals, SSRI, RNA, Messenger, Behavior, Animal, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Brain-Derived Neurotrophic Factor, TrkB, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Rats, Disease Models, Animal, BDNF, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, prenatal stress, Prenatal Exposure Delayed Effects, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SDV.BDD.EO ] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, depression, Female, Neuroplasticity, Selective Serotonin Reuptake Inhibitors, Stress, Psychological
Abstract: International audience; With the growing use of selective serotonin reuptake inhibitor medications (SSRIs) for the treatment of depression during the perinatal period, questions have been raised about the longterm impact of these medications on development. We aimed to investigate how developmental SSRI exposure may alter affect-related behaviors and associated molecular processes in offspring using a rodent model of maternal stress and depression. For this purpose, prenatally stressed or non-stressed male offspring were exposed to fluoxetine (5 mg/kg/day) or vehicle, via lactation, until weaning. Primary results show that postnatal fluoxetine exposure differentially altered anxiety-like behavior by increasing anxiety in non-stressed offspring and decreasing anxiety in prenatally stressed offspring. In the hippocampus, developmental fluoxetine exposure decreased BDNF IV and TrkB mRNA expression. Prenatal stress alone also decreased escape behaviors and decreased hippocampal BDNF IV mRNA expression. These data provide important evidence for the long-term programming effects of early-life exposure to SSRIs on brain and behavior.
Published: 2016
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53. Inhibition of gut- and lung-derived serotonin attenuates pulmonary hypertension in mice

Author: Caroline Chevarin, Amal Houssaini, Valérie Amsellem, Jean-Luc Dubois-Randé, Feng Wan, Guillaume Gary-Bobo, Serge Adnot, Shariq Abid, Nathalie Mouraret, Claire-Marie Tissot, Michel Hamon, Elisabeth Marcos, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR10, Centre de Psychiatrie et Neurosciences (CPN - U894), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Guellaen, Georges
Subjects: Pulmonary and Respiratory Medicine, Serotonin, medicine.medical_specialty, Duodenum, Physiology, Hypertension, Pulmonary, Hemodynamics, Citalopram, transgenic mice, 030204 cardiovascular system & hematology, Biology, serotonin synthesis, Mice, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine.artery, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Hypoxia, Lung, 030304 developmental biology, Serotonin Plasma Membrane Transport Proteins, 0303 health sciences, serotonin transporter, Cell Biology, medicine.disease, Pulmonary hypertension, 3. Good health, Mice, Inbred C57BL, Pyrimidines, Blood pressure, medicine.anatomical_structure, Endocrinology, Adjunctive treatment, Pulmonary artery, tryptophan hydroxylase, Selective Serotonin Reuptake Inhibitors, pulmonary vascular remodeling, medicine.drug
Abstract: International audience; Decreasing the bioavailability of serotonin (5-HT) by inhibiting its biosynthesis may represent a useful adjunctive treatment of pulmonary hypertension (PH). We assessed this hypothesis using LP533401, which inhibits the rate-limiting enzyme tryptophan hydroxylase 1 (Tph1) expressed in the gut and lung, without inhibiting Tph2 expressed in neurons. Mice treated repeatedly with LP533401 (30-250 mg/kg per day) exhibited marked 5-HT content reductions in the gut, lungs, and blood, but not in the brain. After a single LP533401 dose (250 mg/kg), lung and gut 5-HT contents decreased by 50%, whereas blood 5-HT levels remained unchanged, suggesting gut and lung 5-HT synthesis. Treatment with the 5-HT transporter (5-HTT) inhibitor citalopram decreased 5-HT contents in the blood and lungs but not in the gut. In transgenic SM22-5-HTT+ mice, which overexpress 5-HTT in smooth muscle cells and spontaneously develop PH, 250 mg/kg per day LP533401 or 10 mg/kg per day citalopram for 21 days markedly reduced lung and blood 5-HT levels, right ventricular (RV) systolic pressure, RV hypertrophy, distal pulmonary artery muscularization, and vascular Ki67-positive cells (P < 0.001). Combined treatment with both drugs was more effective in improving PH-related hemodynamic parameters than either drug alone. LP533401 or citalopram treatment partially prevented PH development in wild-type mice exposed to chronic hypoxia. Lung and blood 5-HT levels were lower in hypoxic than in normoxic mice and decreased further after LP533401 or citalopram treatment. These results provide proof of concept that inhibiting Tph1 may represent a new therapeutic strategy for human PH.
Published: 2012
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54. Delaying aging and the aging-associated decline in protein homeostasis by inhibition of tryptophan degradation

Author: Ellen A. A. Nollen, Jasper Krijnen, Mariana Ruiz Silva, Rafael P. Vázquez-Manrique, R.C. Buijsman, Helen Michels, Annemieke T. van der Goot, Peter J. Oefner, Christian Neri, Renée I. Seinstra, Francesca Farina, Ronald Melki, Karen L. Thijssen, Wentao Zhu, Katja Dettmer, Ido P. Kema, Departments of Genetics and Laboratory Medicine, University of Groningen, Institute of Functional Genomics (IFG), Universität Regensburg (UR), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Enzymologie et Biochimie Structurales (LEBS), Centre National de la Recherche Scientifique (CNRS), European Research Institute for the Biology of Aging, University of Regensburg, Centre de Psychiatrie et Neurosciences (CPN - U894), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Faculteit Medische Wetenschappen/UMCG, Molecular Neuroscience and Ageing Research (MOLAR), Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Lifestyle Medicine (LM)
Subjects: Aging, Kynurenine pathway, ALPHA-SYNUCLEIN, Metabolite, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Animals, Genetically Modified, chemistry.chemical_compound, 0302 clinical medicine, PARKINSONS-DISEASE, Tandem Mass Spectrometry, MESH: Reverse Transcriptase Polymerase Chain Reaction, Homeostasis, MESH: Aging, MESH: Animals, Kynurenine 3-Monooxygenase, Caenorhabditis elegans, IN-VIVO, LIFE-SPAN, 0303 health sciences, Multidisciplinary, biology, MESH: Immunoblotting, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Reverse Transcriptase Polymerase Chain Reaction, MESH: Peptides, Tryptophan, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Biological Sciences, PROTEOTOXICITY, LEWY BODIES, Tryptophan Oxygenase, MESH: Amyloid beta-Peptides, HEAT-SHOCK-FACTOR, Biochemistry, MESH: Longevity, MESH: Homeostasis, Toxicity, C-ELEGANS, RNA Interference, MESH: Computational Biology, MESH: DNA Primers, Huntington, Immunoblotting, MESH: RNA Interference, MESH: Tryptophan Oxygenase, MESH: Animals, Genetically Modified, 03 medical and health sciences, longevity, MESH: Caenorhabditis elegans, MESH: alpha-Synuclein, Animals, MESH: Tryptophan, DNA Primers, 030304 developmental biology, KYNURENINE 3-MONOOXYGENASE, Alpha-synuclein, Amyloid beta-Peptides, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Computational Biology, MESH: Tandem Mass Spectrometry, MESH: Fertility, biology.organism_classification, Fertility, Proteotoxicity, chemistry, Peptides, CAENORHABDITIS-ELEGANS, MESH: Chromatography, Liquid, 030217 neurology & neurosurgery, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Chromatography, Liquid
Abstract: Toxicity of aggregation-prone proteins is thought to play an important role in aging and age-related neurological diseases like Parkinson and Alzheimer’s diseases. Here, we identify tryptophan 2,3-dioxygenase ( tdo-2 ), the first enzyme in the kynurenine pathway of tryptophan degradation, as a metabolic regulator of age-related α-synuclein toxicity in a Caenorhabditis elegans model. Depletion of tdo-2 also suppresses toxicity of other heterologous aggregation-prone proteins, including amyloid-β and polyglutamine proteins, and endogenous metastable proteins that are sensors of normal protein homeostasis. This finding suggests that tdo-2 functions as a general regulator of protein homeostasis. Analysis of metabolite levels in C. elegans strains with mutations in enzymes that act downstream of tdo-2 indicates that this suppression of toxicity is independent of downstream metabolites in the kynurenine pathway. Depletion of tdo-2 increases tryptophan levels, and feeding worms with extra l -tryptophan also suppresses toxicity, suggesting that tdo-2 regulates proteotoxicity through tryptophan. Depletion of tdo-2 extends lifespan in these worms. Together, these results implicate tdo-2 as a metabolic switch of age-related protein homeostasis and lifespan. With TDO and Indoleamine 2,3-dioxygenase as evolutionarily conserved human orthologs of TDO-2, intervening with tryptophan metabolism may offer avenues to reducing proteotoxicity in aging and age-related diseases.
Published: 2012
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55. Confirmation of the factorial structure of temperamental autoquestionnaire TEMPS-A in non-clinical young adults and relation to current state of anxiety, depression and to schizotypal traits

Author: Marie-Chantal Bourdel, Henri Lôo, Yannick Morvan, Marie-Odile Krebs, Kareen K. Akiskal, Hagop S. Akiskal, Feriel Tibaoui, Université Paris Nanterre (UPN), Clinique, Psychanalyse, Développement (CliPsyD), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Nanterre ( UPN ), Clinique, Psychanalyse, Développement ( CliPsyD ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Male, medicine.medical_specialty, Personality Inventory, Schizotypy, media_common.quotation_subject, Population, [ SCCO.PSYC ] Cognitive science/Psychology, Anxiety, Schizotypal Personality Disorder, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Cronbach's alpha, Surveys and Questionnaires, medicine, Humans, Temperament, education, Psychiatry, ComputingMilieux_MISCELLANEOUS, media_common, education.field_of_study, Depression, Reproducibility of Results, medicine.disease, Schizotypal personality disorder, Confirmatory factor analysis, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, [SCCO.PSYC]Cognitive science/Psychology, Female, medicine.symptom, Personality Assessment Inventory, Factor Analysis, Statistical, Psychology, 030217 neurology & neurosurgery
Abstract: Background The 39-item TEMPS-A self-rated questionnaire assesses affective temperaments. We examined the factorial structure of its French version in a large sample of young adults and examined the relation to schizotypy, depression and anxiety. Method University students were enrolled during their mandatory preventive health visit in the University medical facility (n = 3807, 19.9 ± 2.5 y.o.). They answered to the 39-TEMPS-A questionnaire, the Schizotypal Personality Questionnaire (SPQ) and the Hospital Anxiety Depression Scale (HADS). We performed an exploratory Factorial Component Analysis (FCA) with varimax rotation of the 39-TEMPS-A in half of the sample, randomly selected, followed by a Confirmatory Factor Analysis (CFA) in the remaining subsample. TEMPS-A dimensions were correlated to HADS and SPQ sub-scores. Results A five-factor structure was found by PCA and confirmed by the confirmatory analysis. The scale showed a good internal consistency (whole scale Cronbach's α: 0.83 and from 0.78 to 0.59 for Cyclothymic, Depressive , Irritable , Hyperthymi c, Anxiou s subscales). Depressive and Anxious TEMPS-A subscales were moderately correlated to HADS Depression and Anxiety subscales (Spearman ρ = 0.37 to 0.33). Cyclothymic and Depressive TEMPS-A subscales were respectively correlated to SPQ Paranoid (ρ = 0.53) and Negative dimensions (ρ = 0.52). Limitation Representativity of the sample (higher education, response rate). Conclusion We confirmed the five factor structure of the 39-item TEMPS-A in a large non-clinical population of young adults and found consistent correlations with anxiety — depression state markers and schizotypal traits.
Published: 2011
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56. Continuous enriched environment improves learning and memory in adult NMRI mice through theta burst-related-LTP independent mechanisms but is not efficient in advanced aged animals

Author: Patrick Dutar, Thomas Freret, Valentine Bouet, Jean-Marie Billard, Michel Boulouard, Groupe Mémoire et Plasticité comportementale ( GMPc ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Groupe Mémoire et Plasticité comportementale (GMPc), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mobilités : Vieillissement, Pathologie, Santé (COMETE), and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Aging, Hippocampus, Hippocampal formation, Biology, Synaptic Transmission, Mice, 03 medical and health sciences, 0302 clinical medicine, Animals, Learning, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Environmental enrichment, Neuronal Plasticity, [SCCO.NEUR]Cognitive science/Neuroscience, Glutamate receptor, Long-term potentiation, Cognition, Electrophysiology, Anesthesia, [ SCCO.NEUR ] Cognitive science/Neuroscience, Synaptic plasticity, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Neuroscience, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; INTRODUCTION: Effects of 3-month continuous environmental enrichment (EE) on cognitive abilities and on theta burst-related synaptic plasticity of CA1 hippocampal neuronal networks have been assessed in 6- and 20-month old NMRI female mice. RESULTS: EE decreased anxiety-like behavior and improved learning and memory performances in adult but not in aged mice. Electrophysiological results in CA1 hippocampal slices showed that basal synaptic transmission was not affected by EE in adult mice whereas it was partially improved in aged animals, even though not sufficient to rescue the decrease related to aging. Besides, no effect of EE on N-methyl-d-aspartate receptor activation and theta-burst-induced long-term potentiation was found in adult or aged animals. DISCUSSION: These results indicate that continuous EE is able to improve cognitive abilities in adult NMRI female mice, that does not correlate with changes in theta burst-related synaptic plasticity within neuronal networks. In addition, the lack of effects in aged animals suggests the existence of a critical delay for the beneficial effects of EE on cognitive aging.
Published: 2011
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57. Trouble bipolaire et comorbidités addictives

Author: Y. Le Strat, Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Psychiatrie et Neurosciences (CPN - U894), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5), and Institut de psychiatrie et neurosciences (U894 / UMS 1266)
Subjects: Épidémiologie, Psychiatry and Mental health, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Arts and Humanities (miscellaneous), Facteur de risque, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Effets subjectifs, Addiction, Trouble bipolaire, Applied Psychology
Abstract: International audience; La consommation de toxiques en général, et d'alcool en particulier, est particulièrement importante chez les sujets souffrant de troubles bipolaires. De même, les diagnostics d'abus et de dépendance à l'alcool sont plus élevés chez les sujets souffrant de troubles bipolaires qu'en population générale, et ce dans tous les travaux épidémiologiques. Toutefois, les raisons de cette association frappante entre ces deux troubles restent mal connues. Les principales hypothèses évoquées dans la littérature sont la possibilité d'une automédication par l'alcool, l'implication de facteurs génétiques communs aux deux troubles, ainsi que l'induction du trouble bipolaire par la consommation de toxiques. Toutefois, ces hypothèses ne permettent pas à ce jour d'expliquer l'intensité de l'association trouble bipolaire/alcoolo-dépendance de façon satisfaisante. D'autres hypothèses plus récentes permettent de mieux comprendre les liens neurobiologiques communs sous-tendant ces affections. Après une revue des données épidémiologiques, nous verrons en quoi ces hypothèses peuvent être erronées, justes, ou même complémentaires.
Published: 2010
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58. Long-Lasting Effects of Chronic Intermittent Alcohol Exposure in Adolescent Mice on Object Recognition and Hippocampal Neuronal Activity

Author: Gregory Beaudet, Thomas Freret, Laurence Lanfumey, Michel Boulouard, Véronique Lelong-Boulouard, Joanna Bourgine, Samuel Valable, Eleni Paizanis, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Groupe Mémoire et Plasticité comportementale (GMPc), Normandie Université (NU)-Normandie Université (NU), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Mobilités : Attention, Orientation et Chronobiologie (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Pharmacologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ), Groupe Mémoire et Plasticité comportementale ( GMPc ), Normandie Université ( NU ) -Normandie Université ( NU ), Hypoxie, physiopathologies cérébrovasculaire et tumorale ( CERVOxy ), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales ( ISTCT ), Normandie Université ( NU ) -Normandie Université ( NU ) -Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Mobilités : Attention, Orientation et Chronobiologie ( COMETE ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département de Pharmacologie [Caen], Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Centre de Psychiatrie et Neurosciences (U894)
Subjects: 0301 basic medicine, Male, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Hippocampus, Binge drinking, Prefrontal Cortex, Neuroimaging, Hippocampal formation, Motor Activity, Toxicology, Spatial memory, Binge Drinking, 03 medical and health sciences, Mice, 0302 clinical medicine, Premovement neuronal activity, Animals, Maze Learning, Perirhinal Cortex, Object Recognition, [ SDV ] Life Sciences [q-bio], Ethanol, Working memory, Immediate-Early Genes, Dentate gyrus, Genes, fos, Recognition, Psychology, Spontaneous alternation, Magnetic Resonance Imaging, Psychiatry and Mental health, 030104 developmental biology, Memory, Short-Term, Psychology, Adolescent Intermittent Ethanol Exposure, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND:Binge drinking is popular and highly prevalent in teenagers. However, the long-term cognitive and neurobiological consequences of such practices are not yet fully understood. In this context, we therefore assessed in mice whether a chronic intermittent alcohol (CIA) exposure in adolescence had long-term consequences on object discrimination and memory performances, emotional behaviors, brain activity, and morphology.METHODS:C57BL/6JRj mice were treated with either saline or ethanol (EtOH) (2 g/kg/d, i.p., from postnatal days [PND] 30 to PND 44 every other day). The day following the last administration or later in adulthood (PND 71) mice were tested for different behavioral tests (novel object recognition, spontaneous alternation, light-dark box, elevated plus-maze, actimeter test), to assess object recognition, working memory performances, anxiety-like behavior, and locomotor activity. We also investigated neuronal activation of hippocampus, prefrontal and perirhinal cortices, and anatomical changes using immediate-early gene expression and longitudinal brain magnetic resonance imaging.RESULTS:Our results showed that adolescent mice exposed to CIA present a critical and persistent impairment of short-term object recognition performances. By contrast, spatial working memory was not impaired, nor was anxiety-like behavior. This altered object discrimination was associated with a biphasic change in neuronal activity in the hippocampus but without morphological changes. Indeed, c-Fos expression was specifically increased in the dorsal dentate gyrus (DG) of the hippocampus after the binge exposure, but then became significantly lower in adulthood both in the DG and the CA1 part of the hippocampus compared with adult saline pretreated mice.CONCLUSIONS:These findings provide evidence for adolescent vulnerability to the effects of intermittent binge EtOH exposure on object discrimination and hippocampal activity with long-lasting consequences.
Published: 2015
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59. Papillary glioneuronal tumors: histological and molecular characteristics and diagnostic value of SLC44A1-PRKCA fusion

Author: Ludovic Lacroix, Felipe Andreiuolo, Fabrice Chrétien, Frédéric Fina, Pascale Varlet, Arnault Tauziède-Espariat, Stéphanie Puget, Julia A. Bridge, David Castel, Emmanuèle Lechapt-Zalcman, Xiao Qiong Liu, Estelle Daudigeos-Dubus, Vita Ridola, Marc Polivka, Nathalie Boddaert, Mélanie Pagès, Jacques Grill, Sophie Gilles, Neuroimagerie en psychiatrie (U1000), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Sainte Anne [Paris], Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Hôpital Lariboisière, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Anatomie Pathologique [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Necker - Enfants Malades [AP-HP], University of Nebraska Medical Center, University of Nebraska System, Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lariboisière-Fernand-Widal [APHP], Institut Pasteur [Paris] (IP), Centre de Psychiatrie et Neurosciences (U894), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Centre National de la Recherche Scientifique (CNRS)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Neuroimagerie en psychiatrie ( U1000 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Institut Gustave Roussy ( IGR ), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] ( UMR 8203 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Centre National de la Recherche Scientifique ( CNRS ), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales ( ISTCT ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Laboratoire d'Anatomie Pathologique [Caen], Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Male, Pathology, [SDV]Life Sciences [q-bio], Antigens, CD34, medicine.disease_cause, Ganglioglioma, 0302 clinical medicine, KIAA-BRAF, Child, ganglioglioma, Mutation, medicine.diagnostic_test, Brain Neoplasms, Kinase, Glioma, Magnetic Resonance Imaging, Neoplasms, Neuroepithelial, 3. Good health, angiocentric neuroepithelial tumors, SLC44A1-PRKCA, Child, Preschool, 030220 oncology & carcinogenesis, Immunohistochemistry, Female, Oncogene Fusion, Adult, medicine.medical_specialty, Protein Kinase C-alpha, Adolescent, Organic Cation Transport Proteins, MAP Kinase Signaling System, Papillary glioneuronal tumor, Nerve Tissue Proteins, BRAF, Pathology and Forensic Medicine, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, Western blot, Antigens, CD, medicine, Humans, Receptor, Fibroblast Growth Factor, Type 1, rosette-forming glioneuronal tumors of the fourth ventricle, [ SDV ] Life Sciences [q-bio], business.industry, Research, medicine.disease, MAPK, FGFR1, Neurology (clinical), business, 030217 neurology & neurosurgery, Fluorescence in situ hybridization
Abstract: International audience; INTRODUCTION:Papillary Glioneuronal Tumor (PGNT) is a grade I tumor which was classified as a separate entity in the World Health Organization Classification of the Central Nervous System 2007 in the group of mixed glioneuronal tumors. This tumor is rare and subclassifying PGNT represents a challenge. Recently, a fusion between SLC44A1 and PRKCA which encodes a protein kinase C involved in MAPK signaling pathway has been described in two studies (five cases). The current study aimed at raising the cytogenetic, histological and molecular profiles of PGNT and to determine if SLC44A1-PRKCA fusion represented a specific diagnostic marker to distinguish it from other glioneuronal tumors.RESULTS:We report on four pediatric cases of PGNT, along with clinico-radiologic and immunohistological features for which SLC44A1-PRKCA fusion assessment by fluorescence in situ hybridization, BRAF V600E and FGFR1 mutation by immunohistochemistry and direct DNA sequencing and KIAA1549-BRAF fusion by RT-PCR were performed. MAPK signaling pathway activation was investigated using phospho-ERK immunohistochemistry and western blot. We analyzed fifteen cases of tumors with challenging histological or clinical differential diagnoses showing respectively a papillary architecture or periventricular location (PGNT mimics). fluorescence in situ hybridization analysis revealed a constant SLC44A1-PRKCA fusion signal in all PGNTs. None of PGNT mimics showed the SLC44A1-PRKCA fusion signal pattern. All PGNTs were negative for BRAF V600E and FGFR1 mutation, and KIAA1549-BRAF fusion. Phospho-ERK analysis provides arguments for the activation of the MAPK signaling pathway in these tumors.CONCLUSIONS:Here we confirmed and extended the molecular data on PGNT. These results suggest that PGNT belong to low grade glioma with MAPK signaling pathway deregulation. SLC44A1-PRKCA fusion seems to be a specific characteristic of PGNT with a high diagnostic value and detectable by FISH.
Published: 2015
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60. PAT1 inversely regulates the surface Amyloid Precursor Protein level in mouse primary neurons

Author: Dilsizoglu Senol, Aysegul, Tagliafierro, Lidia, Huguet, Léa, Gorisse-Hussonnois, Lucie, Chasseigneaux, Stéphanie, Allinquant, Bernadette, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biochemistry, Biophysics and General Pathology, University of Naples Federico II, Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by INSERM, Agence Nationale pour la Recherche,Fédération de Recherche pour le Cerveau and TUBITAK (ADS)., Second University of Naples-Caserta, University of Naples Federico II = Università degli studi di Napoli Federico II, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Chasseigneaux, Stephanie, Centre de Psychiatrie et Neurosciences (CPN - U894), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), 2nd University of Naples, Variabilité de réponse aux psychotropes (VariaPsy - U1144), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), and BMC, BMC
Subjects: Cytoplasm, Amino Acid Transport Systems, Cell Survival, [SDV]Life Sciences [q-bio], Protein trafficking, Down-Regulation, Cell Line, Cellular and Molecular Neuroscience, Amyloid beta-Protein Precursor, Mice, mental disorders, Escherichia coli, Animals, Humans, Biotinylation, RNA, Small Interfering, Cells, Cultured, Cerebral Cortex, Neurons, Symporters, fungi, PAT1 protein, Up-Regulation, [SDV] Life Sciences [q-bio], Amyloid precursor protein, Cell membrane, Research Article
Abstract: International audience; AbstractBackgroundThe amyloid precursor protein (APP) is a key molecule in Alzheimer disease. Its localization at the cell surface can trigger downstream signaling and APP cleavages. APP trafficking to the cell surface in neurons is not clearly understood and may be related to the interactions with its partners. In this respect, by having homologies with kinesin light chain domains and because of its capacity to bind APP, PAT1 represents a good candidate.ResultsWe observed that PAT1 binds poorly APP at the cell surface of primary cortical neurons contrary to cytoplasmic APP. Using down and up-regulation of PAT1, we observed respectively an increase and decrease of APP at the cell surface. The increase of APP at the cell surface induced by low levels of PAT1 did not trigger cell death signaling.ConclusionsThese data suggest that PAT1 slows down APP trafficking to the cell surface in primary cortical neurons. Our results contribute to the elucidation of mechanisms involved in APP trafficking in Alzheimer disease.
Published: 2015
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61. Relationship between early language skills and the development of inattention/hyperactivity symptoms during the preschool period: Results of the EDEN mother-child cohort

Author: Jonathan Bernard, Franck Ramus, Hugo Peyre, Regis HANKARD, Blandine De Lauzon-Guillain, CEDRIC GALERA, Xavier FRITEL, Marie-Josephe Saurel-Cubizolles, Johanna Lepeule, Barbara Heude, Judith Van der Waerden, Service Psychiatrie de l'Enfant et de l'Adolescent, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Laboratoire de sciences cognitives et psycholinguistique (LSCP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS), Epidemiologie-Biostatistique [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Psychiatrie de l'enfant et de l'adolescent [CH C. Perrens, Bordeaux], SECOP - centre hospitalier Charles Perrens, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-Hôpital Corentin Celton [Issy-les-Moulineaux], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 6 : ORCHAD - Origines précoces de la santé du développement de l'enfant (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-10-IDEX-0001-02/10-LABX-0087,IEC,Institute of Cognitive Studies of Ecole normale superieure(2010), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-Hôpital Corentin Celton [Issy-les-Moulineaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Psychiatrie et Neurosciences (U894), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), BMC, BMC, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Laboratoire de sciences cognitives et psycholinguistique ( LSCP ), Département d'Etudes Cognitives - ENS Paris ( DEC ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -École des hautes études en sciences sociales ( EHESS ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bordeaux Ségalen [Bordeaux 2], Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -PRES Sorbonne Paris Cité-Hôpitaux Universitaires Paris Ouest - Hôpital Corentin Celton [Issy-les-Moulineaux], Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Equipe 6 : ORCHAD - Origines précoces de la santé du développement de l'enfant ( CRESS - U1153 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and ANR-10-IDEX-0001-02/10-LABX-0087,IEC,Institute of Cognitive Studies of Ecole normale superieure ( 2010 )
Subjects: Male, [SDV]Life Sciences [q-bio], education, Child Behavior, Hyperkinesis, Language Development, Structural equation modeling, Developmental psychology, 03 medical and health sciences, 0302 clinical medicine, Humans, ADHD, 0501 psychology and cognitive sciences, Child, Preschool, Early language, Language, Schools, [ SDV ] Life Sciences [q-bio], 4. Education, 05 social sciences, Mother-Child Relations, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Language development, Attention Deficit Disorder with Hyperactivity, Child, Preschool, Cohort, Female, Psychology, 030217 neurology & neurosurgery, Period (music), Research Article, 050104 developmental & child psychology
Abstract: Background This study aims to examine bidirectional relationships between children’s language skills and Inattention/Hyperactivity (IH) symptoms during preschool. Method Children (N = 1459) from the EDEN mother-child cohort were assessed at ages 3 and 5.5 years. Language skills were evaluated using the WPPSI-III, NEPSY and ELOLA batteries. Children’s behavior, including IH symptoms, was assessed using the parent-rated Strengths & Difficulties Questionnaire (SDQ). Using a Structural Equation Modeling (SEM) approach, we examined the relationship between language skills and IH symptoms, as well as potential mediating processes. Results SEM analyses indicated a small negative effect of language skills at 3 years on ADHD symptoms at 5.5 years after adjusting for IH symptoms at 3 years (β =−0.12, SE = 0.04, p-value = 0.002). Interpersonal difficulties did not mediate the relationship between early language skills and later IH symptoms, nor was this association reduced after adjusting for a broad range of pre- and postnatal environmental factors and performance IQ. Among different language skills, receptive syntax at 3 years was most strongly related to IH symptoms at 5.5 years. Conclusions Poor language skills at age 3 may predict IH symptoms when a child enters primary school. Implications for the understanding and the prevention of the co-occurrence of language disorders and ADHD are discussed. Electronic supplementary material The online version of this article (doi:10.1186/s12888-016-1091-3) contains supplementary material, which is available to authorized users.
Published: 2015
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62. Neopterin acts as an endogenous cognitive enhancer

Author: Rui Daniel Prediger, Valeria P. Carlini, Mariela F Pérez, Raymond Mongeau, Aderbal S. Aguiar, Laurence Lanfumey, Paulo Alexandre de Oliveira, Filipe C. Matheus, Luis Barbeito, Laura Gabach, Karina Ghisoni, Alexandra Latini, Universidade Federal de Santa Catarina [Florianópolis] ( UFSC ), Universidad Nacional de Córdoba [Argentina], Institut Pasteur de Montevideo, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pharmacologie de la circulation cérébrale ( EA 4475 ), Université Paris Descartes - Paris 5 ( UPD5 ), This work was supported by grants from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, 479222/2013-4), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil, PVE: 004_2013 and 88881.062164/2014-01, INCT 189405 16/2014), FAPESC/CNPq (Programa de Apoio a Núcleos de Excelência PRONEX, NENASC Project), SECyT/UNC (Secretaría de Ciencia y Técnica de la Universidad Nacional de Córdoba, Argentina), FonCyT (Fondo para la Investigación Científica y Tecnológica, Argentina) and CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina). Latini A and Prediger R are CNPq fellows (311451/2013-6), Universidade Federal de Santa Catarina [Florianópolis] (UFSC), Réseau International des Instituts Pasteur (RIIP), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pharmacologie de la circulation cérébrale (EA 4475), and Université Paris Descartes - Paris 5 (UPD5)
Subjects: 0301 basic medicine, Male, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Conditioning, Classical, Long-Term Potentiation, Hippocampus, Open field, Behavioral Neuroscience, chemistry.chemical_compound, Mice, 0302 clinical medicine, Neuroinflammation, immune system diseases, Fear conditioning, Nootropic Agents, Mice, Knockout, Behavior, Animal, Neopterin, Long-term potentiation, purl.org/becyt/ford/3.1 [https], Fear, Interleukin-10, Medicina Básica, Inhibition, Psychological, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Knockout mouse, Memory consolidation, purl.org/becyt/ford/3 [https], Psychology, Learning And Memory, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, Immunology, Neurociencias, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Learning and memory, 03 medical and health sciences, Internal medicine, medicine, Avoidance Learning, Animals, Rats, Wistar, Injections, Intraventricular, Memory Consolidation, [ SDV ] Life Sciences [q-bio], Endocrine and Autonomic Systems, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Rats, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, chemistry, Neuroscience, 030217 neurology & neurosurgery
Abstract: Neopterin is found at increased levels in biological fluids from individuals with inflammatory disorders. The biological role of this pteridine remains undefined; however, due to its capacity to increase hemeoxygenase-1 content, it has been proposed as a protective agent during cellular stress. Therefore, we investigated the effects of neopterin on motor, emotional and memory functions. To address this question, neopterin (0.4 and/or 4 pmol) was injected intracerebroventricularly before or after the training sessions of step-down inhibitory avoidance and fear conditioning tasks, respectively. Memory-related behaviors were assessed in Swiss and C57BL/6 mice, as well as in Wistar rats. Moreover, the putative effects of neopterin on motor and anxiety-related parameters were addressed in the open field and elevated plus-maze tasks. The effects of neopterin on cognitive performance were also investigated after intraperitoneal lipopolysaccharide (LPS) administration (0.33 mg/kg) in interleukin-10 knockout mice (IL-10-/-). It was consistently observed across rodent species that neopterin facilitated aversive memory acquisition by increasing the latency to step-down in the inhibitory avoidance task. This effect was related to a reduced threshold to generate the hippocampal long-term potentiation (LTP) process, and reduced IL-6 brain levels after the LPS challenge. However, neopterin administration after acquisition did not alter the consolidation of fear memories, neither motor nor anxiety-related parameters. Altogether, neopterin facilitated cognitive processes, probably by inducing an antioxidant/anti-inflammatory state, and by facilitating LTP generation. To our knowledge, this is the first evidence showing the cognitive enhancer property of neopterin. Fil: Ghisoni, Karina. Universidade Federal de Santa Catarina; Brasil Fil: Aguiar, Aderbal S.. Universidade Federal de Santa Catarina; Brasil Fil: Oliveira, Paulo Alexandre de. Universidade Federal de Santa Catarina; Brasil Fil: Matheus, Filipe Carvalho. Universidade Federal de Santa Catarina; Brasil Fil: Gabach, Laura. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina Fil: Perez, Mariela Fernanda. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina Fil: Carlini, Valeria Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina Fil: Barbeito, Luis. Instituto Pasteur de Montevideo; Uruguay Fil: Mongeau, Raymond. Université Paris Descartes. INSERM UMR. Centre de Psychiatrie et Neurosciences; Francia Fil: Lanfumey, Laurence. Umr S894, Centre de Psychiatrie Et Neurosciences; Francia Fil: Prediger, Rui Daniel. Universidade Federal de Santa Catarina; Brasil Fil: Latini, Alexandra. Universidade Federal de Santa Catarina; Brasil
Published: 2015
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63. Antidepressant short-term and long-term brain effects during self-referential processing in major depression

Author: Walid Choucha, Maritza Jabourian, Najib Allaïli, Judith Laredo, Pauline Delaveau, Philippe Fossati, Cédric Lemogne, Nathalie Girault, Stéphane Lehéricy, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Recherches Internationales Servier (IRIS-Servier), Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service Universitaire de Psychiatrie de l'Adulte et du sujet âgé, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de neuroImagerie de Recherche, Service de psychiatrie adulte [CHU Pitié-Salpêtière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Recherche Translationnelle en Neurosciences, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Psychiatrie et Neurosciences (U894), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL-UPMC, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -CHU Pitié-Salpêtrière [APHP], Institut de Recherches Internationales Servier ( IRIS-Servier ), Centre National de la Recherche Scientifique ( CNRS ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpitaux Universitaires Paris-Ouest (HUPO), Service de psychiatrie adulte, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Service de Neuroradiologie, and CHU Pitié-Salpêtrière [APHP]
Subjects: [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Emotions, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Precuneus, Antidepressant, Severity of Illness Index, 0302 clinical medicine, Long-term, Acetamides, Prefrontal cortex, Brain Mapping, medicine.diagnostic_test, Brain, Middle Aged, Magnetic Resonance Imaging, Antidepressive Agents, Psychiatry and Mental health, medicine.anatomical_structure, Treatment Outcome, Anesthesia, Major depressive disorder, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Psychology, Self-referential processing, medicine.drug, Clinical psychology, Adult, Ventrolateral prefrontal cortex, Neuroscience (miscellaneous), Prefrontal Cortex, Gyrus Cinguli, 03 medical and health sciences, Double-Blind Method, medicine, Agomelatine, Humans, Radiology, Nuclear Medicine and imaging, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Anterior cingulate cortex, Psychiatric Status Rating Scales, Depressive Disorder, Major, Short-term, Anhedonia, medicine.disease, 030227 psychiatry, Functional magnetic resonance imaging (fMRI), [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Functional magnetic resonance imaging, 030217 neurology & neurosurgery
Abstract: International audience; Acute depression is associated with impaired self-referential processing. Antidepressant effects on the neural bases of self-referential processing in depression are unknown. This study aimed to assess short-and long-term effects of agomelatine on these neural bases in depressed patients and the association between pre-treatment brain activation and remission of depression 6 months later. We conducted a randomized double-blind, placebo-controlled, functional magnetic resonance imaging (fMRI) study during an emotional self-referential task, including three scanning sessions (baseline, after 1 week, and after 7 weeks). Twenty-2 five depressed outpatients were included, all treated with agomelatine or placebo for 1 week. Then, all patients received agomelatine for 24 weeks. Fourteen matched healthy volunteers (HV) who received placebo for 1 week were also included. After 7 days, only depressed patients receiving agomelatine significantly deactivated the ventrolateral prefrontal cortex during self-referential processing, as observed in HV at baseline. After 7 weeks, depressed patients significantly increased the activation of the ventral anterior cingulate cortex. Finally dorsomedial prefrontal cortex and precuneus activations at baseline significantly separated remitters from non-remitters at 24 weeks. In depressed patients, agomelatine had short-and long-term effects on brain structures involved in anhedonia and emotional regulation during self-referential processing. Activation of the dorsomedial prefrontal cortex and precuneus could be informative in the development of biomarker-based treatment of major depression.
Published: 2015
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64. Protein interactome mining defines melatonin MT 1 receptors as integral component of presynaptic protein complexes of neurons

Author: Almudena Espin, Pascal Maurice, Petra Tafelmeyer, Ralf Jockers, Abla Benleulmi-Chaachoua, Victoria Wong, Gerald W. Zamponi, Lina Chen, Igor Stagljar, Philippe Delagrange, Michèle Darmon, Igor Jurisica, M. B. Emerit, Kate Sokolina, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Physiology and Pharmacology, University of Calgary-Hotchkiss Brain Institute, Department of Molecular Genetics [Toronto], University of Toronto, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire biochimique, Hybrigenics Sa, Laboratoire de Signalisation et Récepteurs Matriciels (SiRMa), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Fondation Recherche Medicale (Equipe FRM FRMDEQ20130326503 to R.J.), Inserm, CNRS, and by the Canadian Institutes ofHealth Research., ANR-11-LABX-0071,WHO AM I,Determinants de l'Identité : de la molécule à l'individu(2011), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Donnelly Centre [Toronto, ON, Canada], Department of Physiology and Biophysics, University of Calgary, Département des Sciences Expérimentales, Institut de Recherches Internationales Servier, Institut Cochin (UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), University of Calgary - Hotchkiss Brain Institute, Centre de Psychiatrie et Neurosciences (CPN - U894), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Signalisation et Récepteurs Matriciels (SiRMA, CNRS FRE 3481 MEDyC), Université de Reims Champagne-Ardenne (URCA) - SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Picardie Jules Verne (UPJV) - Université de Reims Champagne-Ardenne (URCA) - Université de Picardie Jules Verne (UPJV) - Université de Reims Champagne-Ardenne (URCA) - Centre National de la Recherche Scientifique (CNRS) - Université de Reims Champagne-Ardenne (URCA) - SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Picardie Jules Verne (UPJV) - Université de Reims Champagne-Ardenne (URCA) - Université de Picardie Jules Verne (UPJV) - Université de Reims Champagne-Ardenne (URCA) - Centre National de la Recherche Scientifique (CNRS), ANR-11-LABX-0071_WHOAMI, WHOAMI, Who am I?, ANR-11-IDEX-0005-02/11-LABX-0071, WHO AM I, Determinants de l’Identité : de la molécule à l’individu(2011), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Bos, Mireille, Determinants de l'Identité : de la molécule à l'individu - - WHO AM I2011 - ANR-11-LABX-0071 - LABX - VALID, and Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Presynaptic Terminals, Nerve Tissue Proteins, melatonin, Biology, Neurotransmission, Melatonin receptor, Synapse, Melatonin, 03 medical and health sciences, Pineal gland, Endocrinology, Calcium Channels, N-Type, synapse, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, G protein-coupled receptor, Receptor, melatonin receptor, Receptor, Melatonin, MT1, Brain, 030104 developmental biology, medicine.anatomical_structure, HEK293 Cells, Synaptic plasticity, Neuroscience, medicine.drug
Abstract: International audience; In mammals, the hormone melatonin is mainly produced by the pineal gland with nocturnal peak levels. Its peripheral and central actions rely either on its intrinsic antioxidant properties or on binding to melatonin MT 1 and MT 2 receptors, belonging to the G protein-coupled receptor (GPCR) super-family. Melatonin has been reported to be involved in many functions of the central nervous system such as circadian rhythm regulation, neurotransmission, synaptic plasticity, memory, sleep, and also in Alzheimer's disease and depression. However, little is known about the subcellular localization of melatonin receptors and the molecular aspects involved in neuronal functions of melatonin. Identification of protein complexes associated with GPCRs has been shown to be a valid approach to improve our understanding of their function. By combining proteomic and genomic approaches we built an interactome of MT 1 and MT 2 receptors, which comprises 378 individual proteins. Among the proteins interacting with MT 1 , but not with MT 2 , we identified several presynaptic proteins, suggesting a potential role of MT 1 in neurotransmission. Presynaptic localization of MT 1 receptors in the hypothalamus, striatum, and cortex was confirmed by subcellular fractionation experiments and immunofluorescence microscopy. MT 1 physically interacts with the voltage-gated calcium channel Ca v 2.2 and inhibits Ca v 2.2-promoted Ca 2+ entry in an agonist-independent manner. In conclusion, we show that MT 1 is part of the presynaptic protein network and negatively regulates Ca v 2.2 activity, providing a first hint for potential synaptic functions of MT 1 .
Published: 2015
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65. Self-reference effect on memory in healthy aging, mild cognitive impairment and Alzheimer’s disease: Influence of identity valence

Author: Francis Eustache, Pascale Piolino, Mickaël Laisney, Mona Leblond, Vincent de la Sayette, Géraldine Rauchs, Béatrice Desgranges, Stéphanie Egret, Virginie Lamidey, Gaël Chételat, Neuropsychologie cognitive et neuroanatomie fonctionnelles de la mémoire humaine, Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -École pratique des hautes études ( EPHE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Neurologie [Lisieux], Centre Hospitalier de Lisieux, Service de Neurologie [Caen], CHU Caen-Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Robert Bisson (CH Robert Bisson), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Eustache, Francis
Subjects: Male, Aging, Cognitive Neuroscience, media_common.quotation_subject, Self-concept, Experimental and Cognitive Psychology, Neuropsychological Tests, 050105 experimental psychology, Developmental psychology, Neglect, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Memory, mental disorders, medicine, Personality, Humans, 0501 psychology and cognitive sciences, Cognitive Dysfunction, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Valence (psychology), Positivity effect, Episodic memory, media_common, Self-reference effect, Aged, Aged, 80 and over, 05 social sciences, Recognition, Psychology, Middle Aged, medicine.disease, Self Concept, Neuropsychology and Physiological Psychology, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Disease Progression, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Alzheimer's disease, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract: International audience; The self-reference effect (SRE) has been shown to benefit episodic memory in healthy individuals. In healthy aging, its preservation is acknowledged, but in Alzheimer’s disease (AD), the jury is still out. Furthermore, there has yet to be a study of the SRE in amnestic mild cognitive impairment (aMCI). As self-reference implies subjective self-representations, and positive information enhance memory performance, we set out to examine the effects of 1) material and 2) identity valence on the SRE across the early stages of AD. Twenty healthy older individuals and 40 patients (20 diagnosed with aMCI and 20 diagnosed with mild AD) performed a memory task. Participants had to judge positive and negative personality trait adjectives with reference to themselves or to another person, or else process these adjectives semantically. We then administered a recognition task. Participants also completed a questionnaire on identity valence. Among healthy older individuals, the SRE benefited episodic memory independently of material and identity valence. By contrast, among aMCI patients, we only observed the SRE when the material was positive. When self-referential material was negative, patients’ performance depended on the valence of their self-representations: negative self-representations correlated with poor recognition of negative self-referential adjectives. Finally, performance of patients with mild AD by condition and material valence were too low and inappropriate to be subjected to relevant analyses. The persistence of an SRE for positive adjectives in aMCI suggests the existence of a positivity effect for self-related information, which contributes to wellbeing. The absence of an SRE for negative adjectives, which led aMCI patients to dismiss negative self-related information, could be due to low self-esteem. These results corroborate the mnenic neglect model and point out the importance of the psychoaffective dimension in patients with aMCI, which could constitute a major factor for the preservation of their self-esteem and self-related memory.Keywords: self-reference effect; positivity effect; episodic memory; amnestic mild cognitive impairment; Alzheimer’s disease
Published: 2015
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66. Cholesterol 24-hydroxylase defect is implicated in memory impairments associated with Alzheimer-like Tau pathology

Author: Kristin Michaelsen-Preusse, Sophie Ayciriex, David Blum, Luc Buée, Marie-Claude Potier, Ivan Bièche, Francisco-Jose Fernandez-Gomez, Fathia Djelti, Luce Dauphinot, Jérôme Braudeau, Raphaëlle Caillierez, Nathalie Cartier, Marie-Anne Burlot, Olivier Laprévote, Benoit Gautier, Patrick Dutar, Martin Korte, Mickael Audrain, Brigitte Potier, Nicolas Auzeil, Jennifer Varin, Faculté de Pharmacie de Paris - Université Paris Descartes (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Thérapie génique, Génomique et Epigénomique (U 1169), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Zoological Institute, Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig], Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, physiopathologie et approches thérapeutiques des maladies héréditaires du système nerveux (EA 7331), Inserm U986, Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes adaptatifs : des organismes aux communautés, Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Alzheimer & Tauopathies [JPArc], Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Facultés des sciences pharmaceutiques et biologiques, Laboratoire de Chimie et Toxicologie Analytique et Cellulaire (EA 4463), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris Descartes - Faculté de Pharmacie de Paris ( UPD5 Pharmacie ), Université Paris Descartes - Paris 5 ( UPD5 ), Max Planck Institute for Cell Biology and Genetics, Max-Planck-Institut, Institut des Sciences Analytiques ( ISA ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Université Claude Bernard Lyon 1 ( UCBL ), Thérapie génique, Génomique et Epigénomique ( U 1169 ), Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Technische Universität Braunschweig [Braunschweig], Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génétique, physiopathologie et approches thérapeutiques des maladies héréditaires du système nerveux ( EA 7331 ), Institut National de la Santé et de la Recherche Médicale, Mécanismes adaptatifs : des organismes aux communautés ( MECADEV ), Muséum National d'Histoire Naturelle ( MNHN ) -Centre National de la Recherche Scientifique ( CNRS ), Alzheimer & Tauopathies ( Equipe 1 ), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ) -Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172 ( JPArc ), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Institut de Chimie des Substances Naturelles ( ICSN ), Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Chimie et Toxicologie Analytique et Cellulaire ( EA 4463 ), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique ( CNRS ), Department of Cellular and Systems Neurobiology, Max-Planck-Institut für Neurobiologie, Service MIRCEN ( MIRCEN ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Alzheimer & Tauopathies (Equipe 1), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), and Université Paris-Saclay-Institut de Biologie François JACOB (JACOB)
Subjects: [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hippocampus, Mice, chemistry.chemical_compound, 0302 clinical medicine, Cerebrospinal fluid, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Gliosis, Phosphorylation, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], General Medicine, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, medicine.anatomical_structure, Tauopathies, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Alzheimer's disease, medicine.symptom, medicine.medical_specialty, Amyloid, Central nervous system, Mice, Transgenic, tau Proteins, Biology, 03 medical and health sciences, Alzheimer Disease, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Cholesterol 24-Hydroxylase, Genetics, medicine, Animals, Humans, Cholesterol 24-hydroxylase, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, 030304 developmental biology, Memory Disorders, Cholesterol, medicine.disease, Hydroxycholesterols, Disease Models, Animal, Endocrinology, chemistry, Steroid Hydroxylases, [ CHIM.ANAL ] Chemical Sciences/Analytical chemistry, 030217 neurology & neurosurgery, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract: Alzheimer's disease (AD) is characterized by both amyloid and Tau pathologies. The amyloid component and altered cholesterol metabolism are closely linked, but the relationship between Tau pathology and cholesterol is currently unclear. Brain cholesterol is synthesized in situ and cannot cross the blood-brain barrier: to be exported from the central nervous system into the blood circuit, excess cholesterol must be converted to 24S-hydroxycholesterol by the cholesterol 24-hydroxylase encoded by the CYP46A1 gene. In AD patients, the concentration of 24S-hydroxycholesterol in the plasma and the cerebrospinal fluid are lower than in healthy controls. The THY-Tau22 mouse is a model of AD-like Tau pathology without amyloid pathology. We used this model to investigate the potential association between Tau pathology and CYP46A1 modulation. The amounts of CYP46A1 and 24S-hydroxycholesterol in the hippocampus were lower in THY-Tau22 than control mice. We used an adeno-associated virus (AAV) gene transfer strategy to increase CYP46A1 expression in order to investigate the consequences on THY-Tau22 mouse phenotype. Injection of the AAV-CYP46A1 vector into the hippocampus of THY-Tau22 mice led to CYP46A1 and 24S-hydroxycholesterol content normalization. The cognitive deficits, impaired long-term depression and spine defects that characterize the THY-Tau22 model were completely rescued, whereas Tau hyperphosphorylation and associated gliosis were unaffected. These results argue for a causal link between CYP46A1 protein content and memory impairments that result from Tau pathology. Therefore, CYP46A1 may be a relevant therapeutic target for Tauopathies and especially for AD.
Published: 2015
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67. Factor structure of the French version of the Hypomanic Personality Scale (HPS) in non-clinical young adults

Author: Yannick Morvan, Sarah Terrien, Chrystel Besche-Richard, Nicolas Stefaniak, Cognition, Santé, Société (C2S), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Maison des Sciences Humaines de Champagne-Ardenne (MSH-URCA), Université de Reims Champagne-Ardenne (URCA), Clinique, Psychanalyse, Développement (CliPsyD), Université Paris Nanterre (UPN), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Maison des Sciences Humaines de Champagne-Ardenne (MSH-URCA), Université Paris Nanterre ( UPN ), Clinique, Psychanalyse, Développement ( CliPsyD ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Adult, Male, medicine.medical_specialty, Bipolar Disorder, Psychometrics, Personality Inventory, lcsh:RC435-571, media_common.quotation_subject, Population, [SHS.PSY]Humanities and Social Sciences/Psychology, [ SCCO.PSYC ] Cognitive science/Psychology, Personality Disorders, 03 medical and health sciences, Young Adult, 0302 clinical medicine, lcsh:Psychiatry, medicine, Personality, Humans, Translations, Bipolar disorder, Psychiatry, education, ComputingMilieux_MISCELLANEOUS, media_common, Psychiatric Status Rating Scales, education.field_of_study, Beck Depression Inventory, Reproducibility of Results, medicine.disease, Personality disorders, Confirmatory factor analysis, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Female, Self Report, Personality Assessment Inventory, Psychology, Factor Analysis, Statistical, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Background Hypomanic Personality Scale (HPS) is a self-report questionnaire designed to identify vulnerable individuals at high risk of bipolar disorders in non-clinical samples. Our aim was to identify the factorial structure of HPS in a French non-clinical sample and to compare this with different factor solutions described in the literature. We carried out a survey in a French population using a French version of HPS. Methods A total of 698 participants were included in the study. They completed the HPS, the Schizotypal Personality Questionnaire-Brief (SPQ-B), the Positive And Negative Affect Schedule (PANAS), and the Beck Depression Inventory (BDI-II). We tested the 1, 3 and 4-factor solutions and used a Confirmatory Factor Analysis to compare these with the factor solutions suggested by Rawling et al. and Schalet et al. Results Goodness-of-fit indices showed that Schalet et al.'s solution “fits” our data better than Rawling et al.'s factorial solutions. HPS scores correlated with the PANAS Positive score and the SPQ-B total score. We confirmed the 3-factor structure of the HPS in a large non-clinical population of young adults and found consistent correlations with BDI, affectivity and schizotypal traits.
Published: 2015
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68. Evolution des lésions ischémiques aiguës en IRM de diffusion

Author: Tisserand, Marie, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité, Catherine Oppenheim, Centre de Psychiatrie et Neurosciences (CPN - U894), and Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5)
Subjects: [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Prognosis, Thrombolysis, Accident vasculaire cérébral, Stroke, Perfusion, Diffusion, Magnetic resonance imaging, Penumbra, Pénombre, Pronostic, Imagerie par résonance magnétique, Perfusion-weighted imaging, Diffusion-weighted imaging, Thrombolyse
Abstract: Within the first 24 hours after IV-rtPA, diffusion-weighted ischemic lesions can reverse, remain stable or grow. The aim of this thesis is to study these reversal and growth phenomena, to better understand their pathophysiology and to gain insight into the prognostic value of diffusion lesion volume. Diffusion lesion reversal was reported in animals and humans after arterial recanalization. In our sample of 155 patients, we studied this phenomenon with MRI performed before and 24 hours after thrombolysis using a voxel-based approach. First, we demonstrated that 24 hours diffusion reversal was frequent and sustained on a late MRI (median 54h) for over two-thirds of the voxels. Second, sustained reversal was associated with 24hr neurological improvement (OR=1.15, IC95%[ 1.03-1.27], P=0.008 per 1mL). Animal studies have suggested that white matter is more resistant to ischemia than gray matter. In humans, we confirmed that diffusion lesion reversal was more frequent in white matter than in gray matter and disclosed that white matter voxels were more prone to reverse than gray matter voxels. The amount of white matter in the initial diffusion lesion may therefore be a significant determinant of reversibility. Large diffusion lesion volume is associated with poor outcome. However, revascularization therapy can prevent infarct growth or even promote lesion reversal. It is still unclear whether these treatments are beneficial in patients with large diffusion volumes (≥70mL). In our series including 267 patients with middle cerebral artery stroke treated with thrombolysis, 54 patients had a ≥70mL diffusion volume, of which 12(22%) had a 3 month favorable outcome. Odds-ratio of recanalization for favorable outcome in the ≥70mL group was 4.87 [1.15-20.73], P=0.03 supporting a benefit of recanalization in this subgroup. Diffusion lesions growth is usually located within the ischemic penumbra. We hypothesized that if it occurred beyond its boundaries, it would translate into neurological deterioration. Unexplained early neurological deterioration is frequent (70% of early neurological deteriorations, 7% in our series of 309 thrombolysed patients) and its causes are not well-known (no symptomatic intra cerebral hemorrhage, malignant edema or post-stroke seizure). We confirmed our hypothesis in these patients with diffusion growth beyond the penumbra. This growth occurred in 9 of the 10 studied patients (7-137mL; > 10mL in 8 patients) and it was significantly larger than in the 30 controls with early neurological deterioration (P=0.047). Moreover its topography matched the neurological items that deteriorated. All together, these results contribute to a better understanding of acute ischemic lesions using diffusion-weighted imaging and may offer perspectives to adapt individual patient care.; Après traitement d’un AIC par thrombolyse, les lésions ischémiques en diffusion peuvent être réversibles, stables et/ou progresser. Cette thèse a pour objectif d’étudier en IRM ces phénomènes de réversibilité et de progression, de mieux comprendre leur physiopathologie, et d’appréhender le rôle pronostic du volume des lésions en diffusion. La réversibilité en diffusion a été rapportée après recanalisation artérielle, chez l’animal et chez l’homme. Dans notre cohorte de 155 patients, nous avons étudié ce phénomène par une analyse voxel à voxel sur des IRM avant et 24h après thrombolyse. Nous avons montré que la réversibilité des anomalies en diffusion à 24h était fréquente et surtout persistait sur une IRM plus tardive (médiane 54h) pour plus de 70% des voxels [58.0-85.9], suggérant que ce phénomène n’était pas transitoire. De plus, seule la réversibilité permanente était associée à une amélioration neurologique à 24h (OR=1.15, CI95%[ 1.03-1.27], P=0.008 par mL). La substance blanche a été décrite comme plus résistante à l’ischémie sur des modèles murins. Chez l’homme, nous avons confirmé la prédominance en substance blanche des phénomènes de réversibilité, avec une probabilité de régression plus importante pour un voxel de substance blanche que pour un voxel de substance grise. Ces résultats pourraient aider à identifier avant décision thérapeutique les lésions potentiellement réversibles, c'est-à-dire celles prédominant en substance blanche. Même s’il existe une association entre le volume de lésion en diffusion avant traitement et le pronostic fonctionnel à 3 mois, la réversibilité des lésions pourrait remettre en cause les seuils de volume au-delà desquels une revascularisation pourrait être futile. En effet, en limitant la progression des anomalies en diffusion et en favorisant leur régression, la revascularisation pourrait aussi avoir un impact sur le pronostic fonctionnel des patients avec un large volume lésionnel (≥70mL). Dans une population de 267 patients avec un infarctus de l’artère cérébrale moyenne traités par thrombolyse, 54 avaient un volume en diffusion ≥70mL, dont 12(22%) avaient un pronostic fonctionnel favorable à 3 mois. L’odds-ratio de la recanalisation pour le pronostic fonctionnel favorable dans le groupe ≥70mL était de 4.87 [1.15-20.73], P=0.03 en faveur d’un impact positif de la recanalisation même dans ce groupe. En l’absence de reperfusion, les anomalies en diffusion progressent au sein de la pénombre ischémique. Selon le modèle « core/pénombre », cette progression lésionnelle ne doit pas s’accompagner d’une aggravation neurologique. Nous avons formulé l’hypothèse que si elle survenait au-delà de la pénombre (dans des zones asymptomatiques), elle s’accompagnerait d’une détérioration neurologique. La détérioration neurologique précoce non expliquée (absence de transformation hémorragique, d’œdème malin ou d’autre cause identifiable) est observée chez 7% de nos 309 patients thrombolysés. Nous avons validé l’hypothèse initiale d’une progression des anomalies en diffusion au-delà de la pénombre chez ces patients. Par une analyse voxel à voxel, elle était présente chez 9 cas/10 (7-137mL; > 10mL chez 8 cas), et son volume était significativement supérieur à celui des 30 contrôles sans détérioration précoce (P=0.047). De plus, sa topographie était congruente avec les fonctions neurologiques qui s’étaient détériorées. L’ensemble de ces résultats participe à une meilleure compréhension de l’évolution des lésions ischémiques aiguës en IRM de diffusion et offre des perspectives pour adapter la prise en charge individuelle afin d’améliorer le pronostic fonctionnel.
Published: 2015

69. 3-month outcome prediction after intravenous thrombolysis for acute ischemic stroke

Author: Turc, Guillaume, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité, Jean-Louis Mas, Catherine Oppenheim, STAR, ABES, Centre de Psychiatrie et Neurosciences (CPN - U894), and Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5)
Subjects: Score de rankin, Acute ischemic stroke, Modified rankin scale, Thrombectomie, Prédiction, Prognosis, Thrombolysis, Accident vasculaire cérébral, Stroke, Magnetic resonance imaging, Imagerie par résonance magnétique, Pronostic, Microbleeds, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Thrombolyse, Prediction, Infarctus cérébral, Microsaignements, Thrombectomy, Outcome
Abstract: Intravenous thrombolysis (IVT) is the only licensed drug for acute ischemic stroke (AIS). However, about half of the treated patients do not achieve functional independence at 3 months (mRS>2), mostly due to lack of early recanalization or symptomatic intracranial hemorrhage (sICH). Firstly, we aimed to determine if 3-month outcome (mRS) after IVT can be reliably predicted based on clinical and MRI variables available at admission. Secondly, we assessed the relationships between the clinical course within 24 hours after IVT and 3-month mRS. We collected clinical and MRI data of all patients treated by IVT ≤4.5 hrs for AIS between 2003 and 2015 in Sainte-Anne hospital, Paris. (1) We derived the MRI-DRAGON score, a simple tool consisting of 7 clinical and MRI variables available at admission, which can reliably predict 3-month mRS>2 (c-statistic=0.83 [0.78-0.88]). (2) We then performed an external validation of this score in the Lille cohort, showing good discrimination and calibration of the model, despite an overestimation of the risk of mRS>2 in patients with a high MRI-DRAGON score. (3) Trying to find additional predictors of long-term outcome, we showed that the cerebral microbleed (CMB) burden at baseline was not an independent predictor of 3-month mRS after adjusting for confounding factors (age and hypertension).Furthermore, we assessed the relationships between early clinical course after IVT and 3-month mRS, based on two common clinical events: (4) Firstly, the lack of very early neurological improvement (VENI) 1 hour after IVT, which was observed in 77% patients and strongly associated with 3-month mRS, but did not improve the predictive ability of the model when incorporated into the MRI-DRAGON score. (5) Secondly, early neurological deterioration (END) within 24 hours after IVT, occuring in 14% patients in our systematic review and meta-analysis. (6) In our cohort, the positive predictive value of END for 3-month mRS>2 prediction was 90%. END of undetermined cause (ENDunexplained) accounted for 70% of ENDs, and was associated with no prior use of antiplatelets, proximal artery occlusion, DWI-PWI mismatch volume and lack of recanalization. We proposed a simple score to predict 3-month mRS soon after admission in patients treated by IVT for AIS. It may be used to help therapeutic decisions, by identifying patients likely to achieve 3-month mRS ≤2 after IVT alone. We have also shown that CMB burden before IVT is not an independent predictor or 3-month outcome. We participate in an ongoing international individual patient data meta-analysis to determine whether there is a subgroup of patients with CMBs, which seems to have an independent risk of poor 3-month outcome so important that it might outweigh the expected benefit of IVT. Although lack of VENI 1 hour after IVT is strongly associated with 3-month mRS>2, it doesn’t seem to be specific enough to guide decision-making regarding additional thrombectomy (bridging therapy), and should therefore not delay an endovascular procedure. Finally, our results suggest that a persistent cerebral hypoperfusion contributes to most ENDs. Therefore, many ENDs might be avoided in a near future, given the recent proof of the clear superiority of bridging therapy over IVT alone regarding recanalization. This revolution in acute stroke management leads the way to important clinical research perspectives, such as developing a tool to accurately predict 3-month mRS after bridging therapy. Important research efforts will be needed to develop a personalized treatment algorithm, helping to determine which therapeutic option (bridging therapy, IVT alone, thrombectomy alone, or no recanalization therapy) would be the best for each patient., La thrombolyse intraveineuse (TIV) est le seul traitement médical autorisé à la phase aiguë de l’infarctus cérébral (IC). Malgré ce traitement, un patient sur deux présente un mauvais pronostic fonctionnel à 3 mois (score mRS>2), ce qui s’explique le plus souvent par l’absence de recanalisation précoce ou la survenue d’une hémorragie intracrânienne symptomatique (sICH). Nos objectifs étaient, d’une part, de déterminer s’il est possible d’estimer le pronostic fonctionnel (mRS) 3 mois après TIV à partir de variables cliniques et IRM disponibles à l’admission, et, d’autre part, d’étudier les relations entre l’évolution au cours des premières 24 heures et le mRS à 3 mois. Nous avons collecté les données cliniques et d’IRM de l’ensemble des patients traités par TIV pour un IC≤4h30 entre 2003 et 2015 à l’hôpital Sainte-Anne. (1) Nous avons proposé le score MRI-DRAGON, un outil simple basé sur 7 variables cliniques et IRM disponibles à l’admission, qui permet une prédiction satisfaisante du mRS>2. 3 mois après un IC traité par TIV (c=0,83 [0,78-0,88]). (2) Nous avons ensuite réalisé une validation externe de ce score sur la cohorte du CHRU de Lille, confirmant qu’il présente une discrimination et une calibration satisfaisantes, malgré une surestimation du risque de mRS>2 en cas de score MRI-DRAGON élevé. (3) Afin d’essayer d’améliorer la prédiction, nous avons étudié les relations entre microsaignements (CMBs) sur l’IRM initiale et pronostic fonctionnel, et montré que le nombre de CMBs n’était pas un prédicteur indépendant du mRS à 3 mois, après ajustement sur les facteurs de confusion (âge, HTA). Nous avons par ailleurs étudié les relations entre l’évolution clinique très précoce après TIV et mRS à 3 mois, à partir de deux situations: (4) Premièrement, l’absence d’amélioration neurologique 1 heure après le début de la TIV en cas d’occlusion artérielle proximale, présente chez 77% des patients et fortement associée au mRS à 3 mois, mais qui n’améliorait pas la prédiction par rapport au score MRI-DRAGON. (5) Deuxièmement, l’aggravation neurologique survenant dans les 24 heures après le début de la TIV (END), dont l’incidence au sein de notre revue systématique était de 14%. (6) Au sein de notre cohorte, la valeur prédictive positive de l’END pour le mRS>2 à 3 mois était de 90%. L’END de cause indéterminée représentait 70% des END, et était associé à l’absence d’antiplaquettaire avant l’admission, la présence d’une occlusion artérielle proximale, d’un important mismatch diffusion-perfusion, et l’absence de recanalisation. Nous avons proposé un score simple permettant de prédire dès l’admission le pronostic fonctionnel à 3 mois d’un patient traité par TIV pour IC aigu. Il pourrait être utilisé pour guider la décision thérapeutique en identifiant les patients ayant une forte probabilité de mRS ≤2 après TIV seule. Par ailleurs, notre travail suggère que la prise en compte des CMBs avant TIV ne permet pas d’améliorer la prédiction pronostique, et que l’association entre CMBs et mRS n’est pas indépendante. Nous participons actuellement à une méta-analyse internationale sur données individuelles visant à déterminer si un sous-groupe de patients avec CMBs présente un risque de sICH si important qu’il pourrait annuler le bénéfice attendu de la TIV. Bien que l’absence d’amélioration neurologique à 1 heure soit fortement associée au mRS>2 à 3 mois, elle ne semble pas être un outil suffisamment robuste pour guider la décision d’une thrombectomie complémentaire à la TIV (bridging therapy), et ne doit donc pas retarder le geste endovasculaire. Enfin, nos résultats suggèrent que la majorité des END sont favorisés par la persistance d’une hypoperfusion cérébrale, et qu’une part d’entre eux pourrait être prochainement évitée, depuis la démonstration fin 2014, de la nette supériorité du bridging therapy par rapport à la TIV seule concernant la recanalisation artérielle. (...)
Published: 2015

70. Rôle des sous-types cliniques versus un effet cumulatif dans l'explication des anomalies de la mémoire et de l'hippocampe chez le sujet déprimé

Author: Blandin, Elise, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris VI, Philip Gorwood, Centre de Psychiatrie et Neurosciences (CPN - U894), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5), and STAR, ABES
Subjects: Âge, Hippocampe, Depression, Memory, Dépression, Neuro toxicité, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Mémoire déclarative, Stress, Hippocampus
Abstract: Through its cerebral localization, its anatomical and functional connectivity, the hippocampus is involved in memory (coding and storing) and in emotion regulation. Cell proliferation in the dentate gyrus, new synaptic connections and the modulation of the efficiency of existing synaptic connections by the Long Term Potentiation and Long Term Depression, participate in memory function. Negative retro feedback that the hippocampus has on the hypothalamic-pituitary-adrenal axis allows a regulation of the reaction of the organism to stress it undergoes. Depression can in fact be considered as a state of stress for the organism.Neuron progenitor proliferation and neuronal plasticity are essential characteristics of the hippocampus ‘functioning. The effect of antidepressant therapeutics, medicinal ones as well as electro convulsive therapy, underlies the importance of this characteristic.Concerning more precisely an endogenous subtype of depression, melancholia, numerous genetic factors have been found as being vulnerability factors. Traumatic events, especially during childhood, are at the origin of the expression of this vulnerability.Memory impairments are found inconstantly in relation to depression. The repetitive character of depression, which is pathology with a high rate of recurrence, could explain that these impairments are only found after several depressive episodes. This is a cumulative or quantitative hypothesis. Or, specificities linked to melancholia could make this subtype more neurotoxic and could explain that memory impairments would be linked to melancholia. This is a qualitative hypothesis.Willing to explore the influence of each of these hypotheses, but one of them requiring studying subjects with different lifetimes being depressed and different ages, we first studied the impact of age on memory impairment. Age is not an independent factor explaining worse memory recovery after a depressive episode once remaining symptoms and memory at baseline are controlled for.Studying the respective influence of the quantitative hypothesis and the qualitative hypothesis we found that the lifetime being depressed is correlated to delayed verbal memory impairment and size of the right hippocampus, whereas the score at scale of melancholia is not. However, lifetime being depressed and the rate of melancholia are correlated.Depression appears to be neurotoxic through a cumulative mechanism, each depressive episode being a stress for the organism with a hyper activation of the hypothalamic-pituitary-adrenal axis and a hyper secretion of cortisol. But taking into account the genetic vulnerability factors, which are linked to endogenous subtype of depression, and the kindling hypothesis with smaller and smaller stressful life events preceding a depressive episode, it could be the same subjects that both have depressive episodes with melancholic characteristics and depression with a high rate of recurrence. This is only a statistic correlation between lifetime being depressed and hippocampal atrophy, biological mechanisms explaining causality for this correlation are not yet known. Only a part of the subjects could be exposed to genetic vulnerability and high recurrence of the depressive episodes or depressive episodes could become melancholic after several recurrences. Further research on this topic is needed. Moreover, looking at the high cost of depression and the high influence of life conditions during childhood, maternal care and traumas, special attention must be payed to them., De par sa localisation anatomique, ses connexions anatomiques et fonctionnelles, l’hippocampe est une structure impliquée dans la mémoire (encodage et stockage de l’information) et dans la régulation des émotions. La prolifération des cellules au niveau du gyrus denté, les nouvelles connexions synaptiques et la modulation de l’efficacité des synapses déjà existantes par la Long Term Potentiantion (LTP) et la Long Term Depression (LTD) participent aux fonctions mnésiques. Le rétro-feedback négatif qu’exerce l’hippocampe sur l’axe hypothalamo-hypophyso-surrénalien permet une régulation de la réaction à un stress auquel est soumis l’organisme. La dépression est en outre considérée comme étant un état de stress pour l’organisme.La prolifération de progéniteurs neuronaux, la plasticité neuronale, sont des caractéristiques essentielles du fonctionnement de l’hippocampe. L’effet des traitements antidépresseurs, aussi bien médicamenteux que l’électro-convulsivo-thérapie (ECT) soulignent l’importance de cette caractéristique.Concernant plus particulièrement une forme de dépression dite endogène, la mélancolie, de nombreux facteurs génétiques sont retrouvés comme étant des facteurs de vulnérabilité. Des évènements traumatiques, particulièrement dans l’enfance, sont à l’origine de l’expression de cette vulnérabilité.Des troubles de la mémoire sont retrouvés de manière inconstante en lien avec la dépression. Le caractère répétitif de la dépression, qui est une maladie récurrente, pourrait expliquer que ces troubles mnésiques ne soient retrouvés qu’après plusieurs épisodes dépressifs, il s’agirait d’un caractère cumulatif, quantitatif. Ou bien, les spécificités liées à la mélancolie seraient à l’origine d’une plus grande neuro-toxicité de cette forme de dépression et expliqueraient que les troubles de la mémoire soient liés à ce type d’épisode, de manière cette fois qualitative.Voulant étudier le poids respectif de ces deux hypothèses, l’une impliquant d’étudier des sujets ayant des temps de vie passés en dépression variables et donc des âges variables, et la fonction testée étant la mémoire qui est altérée avec le vieillissement, nous avons tout d’abord étudié l’impact de l’âge. L’âge n’est pas un facteur indépendant pouvant expliquer une moins bonne récupération de la fonction mnésique après un épisode dépressif majeur lorsque sont pris en compte le niveau de performance mnésique de base et les symptômes persistants.L’étude du poids de l’hypothèse qualitative et quantitative a montré que le temps de vie passé en dépression est corrélé à la performance en mémoire déclarative différée et à la taille de l’hippocampe droit, le score de mélancolie ne l’est pas. En revanche temps de vie passé en dépression et score de mélancolie sont corrélés.La dépression apparaît donc être toxique par un mécanisme cumulatif de chaque épisode qui représente un état de stress pour l’organisme avec une hyper activation de l’axe hypothalamo-hypophyso-surrénalien et une sécrétion accrue de cortisol. Mais du fait des facteurs de vulnérabilité génétique, qui sont liés au type endogène de dépression, et à la théorie de l’embrasement, des évènements de stress de moins en moins importants précédant un épisode dépressif majeur, ce pourrait être les mêmes sujets qui sont à la fois soumis à des épisodes dépressifs à caractéristique mélancolique et à un trouble dépressif multi-récurrent. Il s’agit cependant d’une corrélation statistique entre temps de vie passé en dépression et atteinte de l’hippocampe, les mécanismes biologiques de causalité expliquant ce constat ne sont pas connus. Seule une partie de la population pourrait être exposée à une vulnérabilité génétique et à un grand nombre d’épisodes dépressifs, ou bien les épisodes dépressifs pourraient prendre une caractéristique mélancolique après un certain nombre de récurrence. Des recherches dans ce domaine sont à développer.
Published: 2015

71. Modifications of the endosomal compartment in peripheral blood mononuclear cells and fibroblasts from Alzheimer’s disease patients

Author: Charles Duyckaerts, Malaplate-Armand C, Olivier Jl, Marie-Claude Potier, Isabelle Rivals, Marie Sarazin, Michel Bottlaender, Lorraine Hamelin, Hélène Corne, Julien Lagarde, Luce Dauphinot, Bruno Dubois, Kunie Ando, Guillaume Dorothée, G. Fontaine, Cossec Jc, Fabian Corlier, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Equipe de Statistique Appliquée, Ecole Supérieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI ParisTech), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies biliaires, fibrose et cancer du foie (Inserm UMR_S 938), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [APHP], Unité de Recherches Animal et Fonctionnalités des Produits Animaux (URAFPA), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Laboratoire de Biochimie et Biologie Moléculaire, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), Institut d'Imagerie BioMédicale (I2BM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire de Neuropathologie Raymond Escourolle, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Equipe de Statistique Appliquée (UMRS 1158) (ESA), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], HAL-UPMC, Gestionnaire, Centre de Psychiatrie et Neurosciences (U894), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -CHU Pitié-Salpêtrière [APHP], Ecole Supérieure de Physique et de Chimie Industrielles de la Ville de Paris ( ESPCI ParisTech ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Pathologies biliaires, fibrose et cancer du foie ( Inserm UMR_S 938 ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -CHU Saint-Antoine [APHP], Unité de Recherches Animal et Fonctionnalités des Produits Animaux ( URAFPA ), Université de Lorraine ( UL ) -Institut National de la Recherche Agronomique ( INRA ), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] ( IM2A ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Institut d'Imagerie BioMédicale ( I2BM ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, and CHU Pitié-Salpêtrière [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP)-Université Pierre et Marie Curie - Paris 6 ( UPMC )
Subjects: Apolipoprotein E, Male, Pathology, [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Amyloid beta-Peptides -- cerebrospinal fluid, 0302 clinical medicine, Cerebrospinal fluid, Apolipoproteins E -- genetics, Biomarkers -- blood -- cerebrospinal fluid -- metabolism, Aged, 80 and over, 0303 health sciences, Microscopy, Confocal, Sciences bio-médicales et agricoles, Middle Aged, 3. Good health, Psychiatry and Mental health, Endosomes -- pathology, Biomarker (medicine), Original Article, Female, medicine.medical_specialty, Amyloid, Fibroblasts -- pathology, Endosome, Immunocytochemistry, Neuroimaging, tau Proteins, Endosomes, Peripheral blood mononuclear cell, Cognitive Dysfunction -- blood -- diagnosis -- physiopathology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Apolipoproteins E, Alzheimer Disease, medicine, Dementia, Humans, Cognitive Dysfunction, Biological Psychiatry, 030304 developmental biology, Aged, Leukocytes, Mononuclear -- physiology, Amyloid beta-Peptides, business.industry, tau Proteins -- cerebrospinal fluid, Médecine pathologie humaine, Fibroblasts, medicine.disease, Case-Control Studies, Positron-Emission Tomography, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Leukocytes, Mononuclear, Alzheimer Disease -- blood -- diagnosis -- pathology, business, 030217 neurology & neurosurgery, Biomarkers
Abstract: Identification of blood-based biomarkers of Alzheimer's disease (AD) remains a challenge. Neuropathological studies have identified enlarged endosomes in post-mortem brains as the earliest cellular change associated to AD. Here the presence of enlarged endosomes was investigated in peripheral blood mononuclear cells from 48 biologically defined AD patients (25 with mild cognitive impairment and 23 with dementia (AD-D)), and 23 age-matched healthy controls using immunocytochemistry and confocal microscopy. The volume and number of endosomes were not significantly different between AD and controls. However, the percentage of cells containing enlarged endosomes was significantly higher in the AD-D group as compared with controls. Furthermore, endosomal volumes significantly correlated to [C(11)]PiB cortical index measured by positron emission tomography in the AD group, independently of the APOE genotype, but not to the levels of amyloid-beta, tau and phosphorylated tau measured in the cerebrospinal fluid. Importantly, we confirmed the presence of enlarged endosomes in fibroblasts from six unrelated AD-D patients as compared with five cognitively normal controls. This study is the first, to our knowledge, to report morphological alterations of the endosomal compartment in peripheral cells from AD patients correlated to amyloid load that will now be evaluated as a possible biomarker., info:eu-repo/semantics/published
Published: 2015
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72. The psychometric properties of the french version of the personality inventory for DSM-5

Author: Roskam, Isabelle, Galdiolo, Sarah, Hansenne, Michel, Massoudi, Koorosh, Rossier, Jérôme, Gicquel, Ludovic, Rolland, Jean-Pierre, Latzman, Robert D, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche sur le Sport et le Mouvement (CeRSM), Université Paris Nanterre (UPN), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche sur le Sport et le Mouvement ( CeRSM ), Université Paris Nanterre ( UPN ), UCL - SSH/IACS - Institute of Analysis of Change in Contemporary and Historical Societies, and UCL - SSH/IPSY - Psychological Sciences Research Institute
Subjects: Male, Psychometrics, Personality Inventory, lcsh:Medicine, [ SCCO.PSYC ] Cognitive science/Psychology, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Big Five personality traits, Personality traits, lcsh:Science, media_common, Aged, 80 and over, Multidisciplinary, Depression, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Middle Aged, Emotion Cognition et Comportement, Diagnostic and Statistical Manual of Mental Disorders, Adolescent, Adult, Aged, Factor Analysis, Statistical, Female, France, Humans, Models, Psychological, Personality, Personality Disorders/diagnosis, Young Adult, [SCCO.PSYC]Cognitive science/Psychology, Personality Assessment Inventory, Factor analysis, Psychology, Cognitive psychology, Research Article, medicine.medical_specialty, media_common.quotation_subject, Context (language use), DSM-5, medicine, Personality disorders, Psychiatry, French people, lcsh:R, Eigenvalues, medicine.disease, Personality tests, Facet (psychology), lcsh:Q
Abstract: International audience; In the context of the publication of DSM-5, the Personality Inventory for DSM-5 (PID-5) has been proposed as a new dimensional assessment tool for personality disorders. This instrument includes a pool of 220 items organized around 25 facets included in a five-factor second-order domain structure. The examination of the replicability of the trait structure across methods and populations is of primary importance. In view of this need, the main objective of the current study was to validate the French version of the PID-5 among French-speaking adults from a European community sample (N=2,532). In particular, the assumption of unidimensionality of the 25 facet and the five domain scales was tested, as well as the extent to which the five-factor structure of the PID-5 and the DSM-5 personality trait hierarchical structure are replicated in the current sample. The results support the assumption of unidimensionality of both the facets and the domains. Exploratory factor and hierarchical analyses replicated the five-factor structure as initially proposed in the PID-5.
Published: 2015
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73. Neuropsychological heterogeneity in attention deficit / hyperactivity disorder : factors influencing the disorder’s structural correlates

Author: Villemonteix, Thomas, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité, Université libre de Bruxelles (1970-....), Philip Gorwood, Isabelle Massat, Centre de Psychiatrie et Neurosciences (CPN - U894), and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Catéchol-O-méthyltransferase (COMT), Méthylphénidate, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Imagerie cérébrale structurelle, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Gender, Trouble déficit de l’Attention / Hyperactivité, Dysrégulation émotionnelle, Emotional dysregulation, Morphométrie Voxel-à-voxel, Structural Brain Imaging, Catechol-O-methyltransferase (COMT), Methylphenidate, Attention Deficit / Hyperactivity Disorder, Genre, Voxel-Based Morphometry, MRI, IRM
Abstract: Previous models of Attention Deficit / Hyperactivity Disorder (ADHD) such as Barkley’s or Brown’s conceptualized ADHD as essentially a developmental impairment of executive function. Against this view, it is now recognized that ADHD is a heterogeneous disorder, involving multiple deficits and multiple neuronal pathways. Despite this current theoretical framework, most structural brain imaging studies in ADHD have compared groups of children with ADHD with typically developing children, without trying to identify subgroups within the diagnostic category. This approach has yielded heterogeneous findings, possibly due to inter-studies variations in the type and number of comorbidities, the percentage of medicated participants included, the number of girls included, and/or methodological and statistical differences. Patients participating in these studies were also often exposed to methylphenidate, and potential medication effects on grey matter volumes are still unclear in certain brain regions such as the frontal lobe, despite a therapeutic action involving the preferential activation of catecholamine neurotransmission within the prefrontal cortex. In this thesis, we used voxel-based morphometry to study the influence of two important risk factors for the development of comorbid conditions in ADHD. The first of these two factors was gender, and the second a genetic polymorphism of the Catechol-O-methyltransferase gene known to put children with ADHD at risk for developing a conduct disorder (Val158Met). We also compared grey matter volumes in children with ADHD exposed to methylphenidate, never-medicated children with ADHD and typically developing children. These experimental studies were part of a more general discussion of ADHD neuropsychological and neurobiological heterogeneity. In our study exploring the influence of gender on the structural correlates of ADHD, we report for the first time a gender-by-diagnosis interaction, with grey matter volume differences in boys and girls with ADHD in midline cortical structures, involved in emotional regulation and part of the default mode network. We propose that these differences may contribute to explain why girls with ADHD more often develop inattentive and internalizing symptoms, whereas externalizing symptoms are predominant in boys with ADHD. In our study investigating the effects of Val158Met in ADHD, we report the first evidence of a COMT-related genetic modulation of ADHD-related grey matter volume alterations. Indeed, children with ADHD at higher risk for developing a conduct disorder (children homozygotes for the Val158 allele) presented increased grey matter volumes in the caudate nucleus when compared with typically developing children, whereas children carrying a Met158 allele presented with decreased grey matter volumes in the right inferior frontal cortex, a region known for its key role in attention. Finally, we measured grey matter volumes in medicated children with ADHD, never-medicated children with ADHD and typically developing children using both whole-brain voxel-based morphometry and automated tracing procedures in chosen regions of interest. We document potential methylphenidate-related grey matter volume normalization and deviation in previously unexplored frontal and temporal regions, and report a positive association between treatment history and grey matter volume in the nucleus accumbens, a key region for reward processing. Our first two experimental studies therefore contribute to a better understanding of the influence of important sources of within-category heterogeneity, while the third helps clarifying the potential confounding effect of medication exposure in previous structural brain imaging studies in ADHD.; Succédant à une théorisation centrée sur le rôle des déficits des fonctions exécutives, les modèles contemporains du trouble déficit de l'attention / hyperactivité (TDAH) mettent en avant l’hétérogénéité d’une catégorie diagnostique impliquant des déficits neuropsychologiques, voies cérébrales et mécanismes étiopathogéniques multiples. En dépit de cette évolution, la majorité des études d'imagerie cérébrale des corrélats structurels du trouble menées à ce jour ont été conduites au niveau de la catégorie diagnostique, sans spécification supplémentaire. Cette approche comparant en moyenne un groupe de patients avec TDAH à un groupe de sujets sains a donné des résultats très variables d'une étude à l'autre, la comparaison inter-étude étant toutefois rendue difficile par la présence de facteurs confondants, tels que des différences en terme de régions d’intérêt examinées, de comorbidités acceptées chez les patients, de pourcentages de sujets masculins et féminins, de fenêtre d’âge sélectionnée, de méthodologie d'analyse ou encore de pourcentage de patients traités par méthylphénidate. Dans ce doctorat, nous nous sommes appuyés sur la morphométrie voxel-à-voxel pour isoler l’influence sur les volumes de matière grise de deux facteurs d’hétérogénéité intra-catégorielle dans le TDAH : le genre d’une part, et un polymorphisme génétique (Val158Met du gène Catéchol-O-méthyltransferase (COMT)) d’autre part ; ces deux facteurs présentant l’intérêt de moduler le risque associé de développer un trouble de type externalisé. Nous avons également comparé les volumes de matière grise d’enfants avec TDAH ayant reçu un traitement par méthylphénidate, de patients n'ayant jamais été exposé à la médication, et de sujet sains. Ces recherches expérimentales ont été inscrites dans une discussion plus générale de l’hétérogénéité des résultats de la littérature structurelle consacrée au TDAH et des sources neuropsychologiques de cette hétérogénéité. Dans notre étude des effets du genre sur les volumes de matière grise dans le TDAH, nous reportons pour la première fois une interaction entre genre et diagnostic, avec des corrélats structurels du trouble différents chez les garçons et les filles avec TDAH dans des régions de la ligne médiane du cerveau, impliquées à la fois dans la régulation émotionnelle et dans le fonctionnement du mode de réseau par défaut. Nous suggérons que ces différences structurelles pourraient contribuer aux différences de risque associé pour les troubles internalisés et externalisés présentées par les garçons et filles avec TDAH. Dans notre étude explorant l'influence du polymorphisme Val158Met sur les volumes de matière grise, nous mettons en évidence une modulation génétique des corrélats structurels du trouble : les sujets homozygotes pour l'allèle Val158, identifiés dans la littérature comme à risque pour le développement d'un trouble des conduites, présentent des volumes de matière grise supérieurs dans le noyau caudé comparativement aux sujets sains, tandis que les patients avec TDAH porteurs d'un allèle Met158 présentent des volumes de matière grise plus faibles dans le cortex préfrontal inférieur droit, une région cruciale pour les processus de contrôle attentionnel. Enfin, dans notre étude des corrélats structurels de l'exposition au méthylphénidate, nous reportons un effet potentiellement normalisateur du traitement sur les volumes de matière grise de l'insula et du pole temporal, des volumes de matière grise plus faibles chez les patients traités comparativement aux sujets sains dans le gyrus frontal moyen et dans le gyrus précentral, et une association entre volume de matière grise dans le nucleus accumbens gauche et durée d'exposition au méthylphénidate chez les sujets traités. (...)
Published: 2015

74. Targeting the cis-dimerization of LINGO-1 with low MW compounds affects its downstream signalling

Author: Cobret, L, De Tauzia, M L, Ferent, J, Traiffort, E, Hénaoui, I, Godin, F, Kellenberger, E, Rognan, D, Pantel, J, Bénédetti, H, Morisset-Lopez, S, Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherches Cliniques de Montréal ( IRCM ), Université de Montréal ( UdeM ), Stéroides et système nerveux : physiopathologie moléculaire et clinique, Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Innovation Thérapeutique ( LIT ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), MEDALIS Drug Discovery Center, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches Cliniques de Montréal (IRCM), Université de Montréal (UdeM), Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire d'Innovation Thérapeutique (LIT), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Frapart, Isabelle, Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)
Subjects: [SDV] Life Sciences [q-bio], [ SDV ] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: International audience; Background and PurposeThe transmembrane protein LINGO-1 is a negative regulator in the nervous system mainly affecting axonal regeneration, neuronal survival, oligodendrocyte differentiation and myelination. However, the molecular mechanisms regulating its functions are poorly understood. In the present study, we investigated the formation and the role of LINGO-1 cis-dimers in the regulation of its biological activity.Experimental ApproachLINGO-1 homodimers were identified in both HEK293 and SH-SY5Y cells using co-immunoprecipitation experiments and BRET saturation analysis. We performed a hypothesis-driven screen for identification of small-molecule protein–protein interaction modulators of LINGO-1 using a BRET-based assay, adapted for screening. The compound identified was further assessed for effects on LINGO-1 downstream signalling pathways using Western blotting analysis and AlphaScreen technology.Key ResultsLINGO-1 was present as homodimers in primary neuronal cultures. LINGO-1 interacted homotypically in cis-orientation and LINGO-1 cis-dimers were formed early during LINGO-1 biosynthesis. A BRET-based assay allowed us to identify phenoxybenzamine as the first conformational modulator of LINGO-1 dimers. In HEK-293 cells, phenoxybenzamine was a positive modulator of LINGO-1 function, increasing the LINGO-1-mediated inhibition of EGF receptor signalling and Erk phosphorylationConclusions and ImplicationsOur data suggest that LINGO-1 forms constitutive cis-dimers at the plasma membrane and that low MW compounds affecting the conformational state of these dimers can regulate LINGO-1 downstream signalling pathways. We propose that targeting the LINGO-1 dimerization interface opens a new pharmacological approach to the modulation of its function and provides a new strategy for drug discovery.
Published: 2015
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75. Sulcus Identification and Labeling

Author: Clara Fischer, Denis Rivière, Arnaud Cachia, Julien Lefèvre, Grégory Operto, Matthieu Perrot, Jean-François Mangin, Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre d'Acquisition et de Traitement des Images [Paris], Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Neuroimagerie Assistée par Ordinateur (LNAO), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurosciences de la Timone (INT), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Arthur W. Toga, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Psychiatrie et Neurosciences (U894), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Laboratoire de Neuroimagerie Assistée par Ordinateur ( LNAO ), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -CHU Pitié-Salpêtrière [APHP], Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Institut de Neurosciences de la Timone ( INT ), and Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: [ INFO ] Computer Science [cs], Computer science, business.industry, Pattern recognition, Top-down and bottom-up design, Sulcus, Computational anatomy, 030218 nuclear medicine & medical imaging, [SPI.AUTO]Engineering Sciences [physics]/Automatic, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, [ SPI.AUTO ] Engineering Sciences [physics]/Automatic, medicine, Computer vision, [INFO]Computer Science [cs], Artificial intelligence, Cortical surface, business, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS
Abstract: The complexity and the variability of the cortical folding pattern are overwhelming for human experts. Computational anatomy helps the field to harness the folding variability considered as a proxy for architectural variability. First, bottom-up processing pipelines convert the implicit encoding of the cortical folding pattern embedded in the geometry of the cortical surface into a synthetic graphic representation. Then, learning-based pattern recognition methods assemble the building blocks of the folding making up this representation in order to reconstruct the sulci of the standard nomenclature. Some attempts at improving current folding models using the same bottom-up strategy could have some impact in the near future.
Published: 2015

76. Validity of Shape as a Predictive Biomarker of Final Infarct Volume in Acute Ischemic Stroke

Author: Salvador Pedraza, Norbert Nighoghossian, Jean-Claude Baron, Mathilde Giacalone, Yves Berthezène, T.-H. Cho, Anaïs Rouanet, David Rousseau, Jens Fiehler, Carole Frindel, Marlène Wiart, Leif Østergaard, Images et Modèles, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Physiology and Nuclear Medicine, Aarhus University Hospital, Departments of Diagnostic and Interventional Neuroradiology, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Radiology Department, Hospital Dr Josep Trueta, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales (MOTIVATE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Aarhus University Hospital?Skejby, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] ( UKE ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales ( MOTIVATE )
Subjects: Male, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, Lesion volume, Imaging data, Brain Ischemia, 030218 nuclear medicine & medical imaging, Lesion, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Thrombolytic Therapy, Acute ischemic stroke, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Aged, Predictive biomarker, Aged, 80 and over, Advanced and Specialized Nursing, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Cerebral Infarction, Thrombolysis, Middle Aged, Prognosis, Surgery, Stroke, Diffusion Magnetic Resonance Imaging, Infarct volume, Disease Progression, Cardiology, Female, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, Biomarkers, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Background and Purpose— This study examines whether lesion shape documented on magnetic resonance diffusion-weighted imaging during acute stroke improves the prediction of the final infarct volume compared with lesion volume only. Methods— Diffusion-weighted imaging data and clinical information were retrospectively reviewed in 110 consecutive patients who underwent (n=67) or not (n=43) thrombolytic therapy for acute ischemic stroke. Three-dimensional shape analysis was performed on admission diffusion-weighted imaging data and 5 shape descriptors were developed. Final infarct volume was measured on T2-fluid-attenuated inversion recovery imaging data performed 30 days after stroke. Results— Shape analysis of acute ischemic lesion and more specifically the ratio of the bounding box volume to the lesion volume before thrombolytic treatment improved the prediction of the final infarct for patients undergoing thrombolysis ( R 2 =0.86 in model with volume; R 2 =0.98 in model with volume and shape). Conclusions— Our findings suggest that lesion shape contains important predictive information and reflects important environmental factors that might determine the progression of ischemia from the core.
Published: 2015
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77. Emotional specificities of autobiographical memory after breast cancer diagnosis

Author: Francis Eustache, Pascale Piolino, Florence Joly, Jacques Dayan, Armelle Viard, Bénédicte Giffard, Djellila Allouache, Nastassja Morel, Sabine Noal, Christelle Levy, Neuropsychologie cognitive et neuroanatomie fonctionnelles de la mémoire humaine, Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -École pratique des hautes études ( EPHE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service Psychiatrie de l'Enfant et de l'Adolescent, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Hôpital Guillaume Régnier, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire Mémoire et Cognition, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Département d'Oncologie Médicale, CHU Caen-Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ), Cancers et préventions, Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pontchaillou [Rennes], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie médicale [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Eustache, Francis, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Guillaume Régnier
Subjects: Coping (psychology), Memory, Episodic, Emotions, Experimental and Cognitive Psychology, Breast Neoplasms, Newly diagnosed, Anxiety, Life Change Events, Breast cancer, Cognition, breast cancer, Arts and Humanities (miscellaneous), Adaptation, Psychological, Developmental and Educational Psychology, medicine, Humans, In patient, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, Autobiographical memory, autobiographical memory, Middle Aged, medicine.disease, Self Concept, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, period of diagnosis, Psychology, Psychosocial, self-representations, Clinical psychology, state anxiety
Abstract: International audience; Cancer involves stressful events. One aspect of cognition that is impacted by stress is episodic autobiographical memory (EAM). EAM is intimately linked to self-representation. Some studies have revealed impairment of EAM in patients with breast cancer in remission. Yet, these studies failed to differentiate between the influence of adjuvant treatments and that of psychosocial factors. We therefore assessed the psychological impact of breast cancer diagnosis on EAM and self-representation profiles prior to any adjuvant treatment. Patients newly diagnosed with breast cancer (n=31) and women without any history of cancer (n=49) were compared on state anxiety, EAM and its emotional characteristics, and self-representations. The most anxious patients retrieved fewer emotional details for memories than the controls, and had lower self-representation scores than the least anxious patients, who had no deficits in emotional detail retrieval. Our results revealed distinct EAM profiles for patients, reflecting two contrasting modes of coping with breast cancer.
Published: 2015
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78. Preservation of Person-Specific Semantic Knowledge in Semantic Dementia: Does Direct Personal Experience Have a Specific Role?

Author: Julie Anne Péron, Pascale ePiolino, Sandrine eLe Moal-Boursiquot, Isabelle eBiseul, Emmanuelle eLeray, Laetitia eBon, Béatrice eDesgranges, Francis eEustache, Serge eBelliard, University of Geneva [Switzerland], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Université Sorbonne Paris Cité (USPC), Université Paris Descartes - Paris 5 (UPD5), CHU Pontchaillou [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), École des Hautes Études en Santé Publique [EHESP] (EHESP), Neuropsychologie et imagerie de la mémoire humaine (NIMH), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], Laboratoire Mémoire, Cerveau et Cognition (LMC2 - EA 7536), Normandie Université (NU)-Normandie Université (NU)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychologie cognitive et neuroanatomie fonctionnelles de la mémoire humaine, Service de Neurologie [CHU Rennes], Institut des Neurosciences Cliniques de Rennes (INCR)-CHU Pontchaillou [Rennes]-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Universitaire de France ( IUF ), Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. ), Department of Epidemiology, EHESP Rennes, Comportement et noyaux gris centraux [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université européenne de Bretagne ( UEB ) -CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -École pratique des hautes études ( EPHE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Neurologie, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Genève = University of Geneva (UNIGE), and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: Personally familiar names, Exploratory research, Semantic dementia, personal experience, Self, famous names, 050105 experimental psychology, lcsh:RC321-571, [SHS]Humanities and Social Sciences, 03 medical and health sciences, Behavioral Neuroscience, [SCCO]Cognitive science, 0302 clinical medicine, self, ddc:150, medicine, Semantic memory, 0501 psychology and cognitive sciences, Relevance (information retrieval), Personal experience, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Original Research, [ SDV ] Life Sciences [q-bio], Recall, Autobiographical memory, semantic memory, 05 social sciences, autobiographical memory, Famous names, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, medicine.disease, personally familiar names, ddc:128.37, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, Neurology, semantic dementia, Direct experience, Psychology, Social psychology, 030217 neurology & neurosurgery, Neuroscience, Cognitive psychology, Meaning (linguistics)
Abstract: International audience; Semantic dementia patients seem to have better knowledge of information linked to the self. More specifically, despite having severe semantic impairment, these patients show that they have more general information about the people they know personally by direct experience than they do about other individuals they know indirectly. However, the role of direct personal experience remains debated because of confounding factors such as frequency, recency of exposure, and affective relevance. We performed an exploratory study comparing the performance of five semantic dementia patients with that of 10 matched healthy controls on the recognition (familiarity judgment) and identification (biographic information recall) of personally familiar names vs. famous names. As expected, intergroup comparisons indicated a semantic breakdown in semantic dementia patients as compared with healthy controls. Moreover, unlike healthy controls, the semantic dementia patients recognized and identified personally familiar names better than they did famous names. This pattern of results suggests that direct personal experience indeed plays a specific role in the relative preservation of person-specific semantic meaning in semantic dementia. We discuss the role of direct personal experience on the preservation of semantic knowledge and the potential neurophysiological mechanisms underlying these processes
Published: 2015
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79. Les interventions sur Internet, destinées aux étudiants souffrant de binge drinking. Revue de la littérature

Author: Lucia Romo, Alexandra Dereux, Marie Vrillon, Philip Gorwood, Laurence Kern, HAL Nanterre, Administrateur, Clinique, Psychanalyse, Développement (CliPsyD), Université Paris Nanterre (UPN), Centre de Recherche sur le Sport et le Mouvement (CeRSM), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, Hôpital Sainte-Anne-Université Paris Descartes - Paris 5 (UPD5), Clinique, Psychanalyse, Développement ( CliPsyD ), Université Paris Nanterre ( UPN ), Centre de Recherche sur le Sport et le Mouvement ( CeRSM ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Clinique des maladies mentales et de l'encéphale ( CMME - Service de psychiatrie ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Hôpital Sainte-Anne
Subjects: [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, 05 social sciences, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SHS.PSY]Humanities and Social Sciences/Psychology, [ SCCO.PSYC ] Cognitive science/Psychology, 050109 social psychology, General Medicine, 030227 psychiatry, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SHS.PSY] Humanities and Social Sciences/Psychology, [ SHS.PSY ] Humanities and Social Sciences/Psychology, 03 medical and health sciences, 0302 clinical medicine, [SCCO.PSYC]Cognitive science/Psychology, [SCCO.PSYC] Cognitive science/Psychology, 0501 psychology and cognitive sciences, [No keyword], ComputingMilieux_MISCELLANEOUS
Abstract: Le binge drinking (consommation ponctuelle importante d’alcool) est un mode de consommation d’alcool frequemment utilise par les etudiants. Les consequences d’une consommation excessive sont nombreuses et il est important d’aider les jeunes qui en souffrent. Les interventions sur Internet (IBI) semblent etre une methode efficace pour les aider a prendre conscience de la dangerosite du binge drinking. Les bases de donnees Medline et PsycINFO ont ete consultees pour effectuer cette revue de la litterature. Le composant principal des IBI est le compte rendu personnalise, accompagne d’informations, de comparaisons normatives, de conseils, etc. Les IBI analysees ont, dans l’ensemble, ete efficaces sur la population etudiante. Malgre une efficacite averee et de nombreux avantages, ce type d’intervention est peu repandu et doit encore se developper, afin de mieux s’adapter aux jeunes.
Published: 2015

80. Cognitive remediation therapy (CRT) benefits more to patients with schizophrenia with low initial memory performances

Author: Chloé Duboc, Yannick Morvan, Aimé Grosz, Caroline Demily, Benoit Pillet, Raphaël Gaillard, Aurélia Todd, Corinne Launay, Isabelle Amado, Nicolas Franck, Marie-Odile Krebs, Université Paris Nanterre (UPN), Clinique, Psychanalyse, Développement (CliPsyD), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Département de Chimie Moléculaire - Chimie Inorganique Redox Biomimétique (DCM - CIRE), Département de Chimie Moléculaire (DCM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Joseph Fourier - Grenoble 1 (UJF), Neuroimagerie cognitive (LCogn), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service hospitalo-universitaire de santé mentale et de thérapeutique, CHU Paris, Université Paris Nanterre ( UPN ), Clinique, Psychanalyse, Développement ( CliPsyD ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre National de la Recherche Scientifique ( CNRS ), Département de Chimie Moléculaire - Chimie Inorganique Redox Biomimétique ( DCM - CIRE ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut de Chimie Moléculaire de Grenoble (ICMG)-Centre National de la Recherche Scientifique ( CNRS ), Neuroimagerie cognitive ( LCogn ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département de Chimie Moléculaire - Chimie Inorganique Redox (DCM - CIRE), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Psychiatrie et Neurosciences (U894), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie Moléculaire de Grenoble (ICMG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: Adult, Male, medicine.medical_specialty, [ SCCO.PSYC ] Cognitive science/Psychology, Neuropsychological Tests, Audiology, Verbal learning, behavioral disciplines and activities, Executive Function, Cognition, InformationSystems_MODELSANDPRINCIPLES, Memory span, medicine, Humans, Attention, Cognitive Behavioral Therapy, Working memory, Rehabilitation, Cognitive flexibility, Middle Aged, Verbal Learning, Executive functions, 3. Good health, Diagnostic and Statistical Manual of Mental Disorders, Memory, Short-Term, Cognitive remediation therapy, [SCCO.PSYC]Cognitive science/Psychology, Schizophrenia, Female, Verbal memory, Cognition Disorders, Psychology, Clinical psychology
Abstract: International audience; Purpose: Cognitive deficits in schizophrenia mainly affect memory, attention and executive functions. Cognitive remediation is a technique derived from neuropsychology, which aims to improve or compensate for these deficits. Working memory, verbal learning, and executive functions are crucial factors for functional outcome. Our purpose was to assess the impact of the cognitive remediation therapy (CRT) program on cognitive difficulties in patients with schizophrenia, especially on working memory, verbal memory, and cognitive flexibility. Methods: We collected data from clinical and neuropsychological assessments in 24 patients suffering from schizophrenia (Diagnostic and Statistical Manual of mental Disorders-Fourth Edition, DSM-IV) who followed a 3-month (CRT) program. Verbal and visuo-spatial working memory, verbal memory, and cognitive flexibility were assessed before and after CRT. Results: The Wilcoxon test showed significant improvements on the backward digit span, on the visual working memory span, on verbal memory and on flexibility. Cognitive improvement was substantial when baseline performance was low, independently from clinical benefit. Conclusions: CRT is effective on crucial cognitive domains and provides a huge benefit for patients having low baseline performance. Such cognitive amelioration appears highly promising for improving the outcome in cognitively impaired patients.
Published: 2015
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81. Identity of the NMDA receptor coagonist is synapse specific and developmentally regulated in the hippocampus

Author: Le Bail, Matildé, Martineau, Magalie, Sacchi, Silvia, Yatsenko, Natalia, Radzishevsky, Inna, Conrod, Sandrine, Ouares, Karima Ait, Wolosker, Herman, Pollegioni, Loredano, Billard, Jean Marie, Mothet, Jean Pierre, Snyder, Solomon H., Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Westfälische Wilhelms-Universität Münster (WWU), Universitá degli Studi dell’Insubria, Rappaport faculty of Medicine, Technion - Israel Institute of Technology [Haifa], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellular Biophysics, Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Department of Biotechnology and Molecular Sciences, Centre de recherche en neurobiologie - neurophysiologie de Marseille ( CRN2M ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] ( LIPhy ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Centre de Psychiatrie et Neurosciences (U894), and Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: Male, [SDV]Life Sciences [q-bio], Long-Term Potentiation, Glycine, Hippocampus, Hippocampal formation, Biology, Receptors, N-Methyl-D-Aspartate, NMDA receptors, Synapse, Glutamatergic, mental disorders, Receptors, Serine, Animals, Hippocampal, CA1 Region, Hippocampal, ComputingMilieux_MISCELLANEOUS, Neurons, Multidisciplinary, [ SDV ] Life Sciences [q-bio], Coagonist, Developmental switch, Animals, Newborn, Astrocytes, Dentate Gyrus, Rats, Synapses, Dentate gyrus, musculoskeletal, neural, and ocular physiology, CA1 Region, Long-term potentiation, Newborn, nervous system, PNAS Plus, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], NMDA receptor, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, N-Methyl-D-Aspartate
Abstract: International audience; NMDA receptors (NMDARs) require the coagonists D-serine or glycine for their activation, but whether the identity of the coagonist could be synapse specific and developmentally regulated remains elusive. We therefore investigated the contribution of D-serine and glycine by recording NMDAR-mediated responses at hippocampal Schaffer collaterals (SC)-CA1 and medial perforant path-dentate gyrus (mPP-DG) synapses in juvenile and adult rats. Selective depletion of endogenous coagonists with enzymatic scavengers as well as pharmacological inhibition of endogenous D-amino acid oxidase activity revealed that D-serine is the preferred coagonist at SC-CA1 mature synapses, whereas, unexpectedly, glycine is mainly involved at mPP-DG synapses. Nevertheless, both coagonist functions are driven by the levels of synaptic activity as inferred by recording long-term potentiation generated at both connections. This regional compartmentalization in the coagonist identity is associated to different GluN1/GluN2A to GluN1/GluN2B subunit composition of synaptic NMDARs. During postnatal development, the replacement of GluN2B- by GluN2A-containing NMDARs at SC-CA1 synapses parallels a change in the identity of the coagonist from glycine to D-serine. In contrast, NMDARs subunit composition at mPP-DG synapses is not altered and glycine remains the main coagonist throughout postnatal development. Altogether, our observations disclose an unprecedented relationship in the identity of the coagonist not only with the GluN2 subunit composition at synaptic NMDARs but also with astrocyte activity in the developing and mature hippocampus that reconciles the complementary functions of D-serine And Glycine In Modulating Nmdars During The Maturation Of Tripartite Glutamatergic Synapses.
Published: 2015
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82. A meta-analysis of the anterior cingulate contribution to social pain

Author: Nathalie George, Pascal Huguet, Eric Tartour, Ouriel Grynszpan, Jean-Yves Rotge, Philippe Fossati, Sophie Hinfray, Cédric Lemogne, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service Universitaire de Psychiatrie de l'Adulte et du sujet âgé, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire de psychologie cognitive (LPC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut des Systèmes Intelligents et de Robotique (ISIR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Provence - Aix-Marseille 1 - Aix Marseille Université (AMU) - Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC) - Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC), Hôpital Européen Georges Pompidou [APHP] (HEGP) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immunologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Européen Georges Pompidou (HEGP), Institut du Cerveau et de la Moëlle Epinière (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC) - Institut National de la Santé et de la Recherche Médicale (INSERM) - CHU Pitié-Salpêtrière [APHP] - Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [APHP], Unité de recherche clinique intersectorielle du Centre Hospitalier Henri Laborit, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpitaux Universitaires Paris-Ouest (HUPO), Centre de Psychiatrie et Neurosciences (CPN), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5) - Université Pierre et Marie Curie - Paris 6 (UPMC), Service de psychiatrie adulte [CHU Pitié-Salpêtière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de psychiatrie adulte, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -CHU Pitié-Salpêtrière [APHP], Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpitaux Universitaires Paris-Ouest (HUPO), Laboratoire de psychologie cognitive ( LPC ), Centre National de la Recherche Scientifique ( CNRS ) -Aix Marseille Université ( AMU ), Institut des Systèmes Intelligents et de Robotique ( ISIR ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: Adult, Cognitive Neuroscience, Pain, [ SCCO.PSYC ] Cognitive science/Psychology, Experimental and Cognitive Psychology, Social Environment, Gyrus Cinguli, behavioral disciplines and activities, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Midcingulate cortex, medicine, Humans, 0501 psychology and cognitive sciences, Child, Anterior cingulate cortex, Cerebral Cortex, Neural correlates of consciousness, medicine.diagnostic_test, 05 social sciences, Social environment, Original Articles, General Medicine, Magnetic Resonance Imaging, Distress, medicine.anatomical_structure, Cerebral cortex, Meta-analysis, [SCCO.PSYC] Cognitive science/Psychology, [SCCO.PSYC]Cognitive science/Psychology, Functional magnetic resonance imaging, Psychology, Neuroscience, psychological phenomena and processes, 030217 neurology & neurosurgery, Clinical psychology
Abstract: International audience; Many functional magnetic resonance imaging studies have explored the neural correlates of social pain that results from social threat, exclusion, rejection, loss or negative evaluation. Although activations have consistently been reported within the anterior cingulate cortex (ACC), it remains unclear which ACC subdivision is particularly involved. To provide a quantitative estimation of the specific involvement of ACC subdivisions in social pain, we conducted a voxel-based meta-analysis. The literature search identified 46 articles that included 940 subjects, the majority of which used the cyberball task. Significant likelihoods of activation were found in both the ventral and dorsal ACC for both social pain elicitation and self-reported distress during social pain. Self-reported distress involved more specifically the subgenual and pregenual ACC than social pain-related contrasts. The cyberball task involved the anterior midcingulate cortex to a lesser extent than other experimental tasks. During social pain, children exhibited subgenual activations to a greater extent than adults. Finally, the ventro-dorsal gradient of ACC activations in cyberball studies was related to the length of exclusion phases. The present meta-analysis contributes to a better understanding of the role of ACC subdivisions in social pain, and it could be of particular importance for guiding future studies of social pain and its neural underpinnings.
Published: 2015
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83. Historic note on Henri Pieron's election at the college de France (1923)

Author: Serge Nicolas, Pascale Piolino, Valérie Gyselinck, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Psychologie des Comportements et des Mobilités (IFSTTAR/AME/LPC), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), Centre de Psychiatrie et Neurosciences (CPN - U894), and Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5)
Subjects: [SHS.HISPHILSO]Humanities and Social Sciences/History, Philosophy and Sociology of Sciences, Arts and Humanities (miscellaneous), [SHS.HISPHILSO] Humanities and Social Sciences/History, Philosophy and Sociology of Sciences, PSYCHOLOGIE, ENSEIGNEMENT, Sociology, HISTOIRE, Humanities, General Psychology
Abstract: The College de France was the first university-level institution to actually recognize psychology as an academic subject (Ribot in 1888 and Janet in 1902). We present here a historical note on the introduction of Henri Piéron at the Collège de France in 1923. The objective of this paper is to describe, on the basis of available historical documents, the events that led to the creation of the chair of 'Physiology of Sensation'. We underline the important roles played by Pierre Janet and Jean Nageotte in this creationand we describe the events that took place at the Collège de France.; Le Collège de France fut la première institution de l'enseignement supérieur à reconnaître officiellement la psychologie (Ribot en 1888 et Janet en 1902). Nous présentons ici une note historique sur l'introduction en 1923 de Henri Piéron au Collège de France. L'objectif de cet article est de décrire, sur la base des documents historiques disponibles, les éÎnements qui ont conduit à la création de la chaire de « Physiologie des sensations ». Nous avons souligné le rôle important de Pierre Janet et Jean Nageotte dans cette création et nous avons présenté en résumé les éÎnements qui se sont déroulés au Collège de France.
Published: 2015
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84. Family-based association study of common variants, rare mutation study and epistatic interaction detection in HDAC genes in schizophrenia

Author: Bruno Millet, Nematollah Jaafari, Amirthagowri Ambalavanan, Boris Chaumette, Lourdes Fañanás, Caroline Dubertret, Lynn E. DeLisi, Ridha Joober, Lan Xiong, Guy A. Rouleau, Douglas F. Levinson, Fayçal Mouaffak, Nicolas Ramoz, Mar Fatjó-Vilas, Oussama Kebir, Marie-Odile Krebs, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center of Excellence in Neuroscience, CHU de Montréal, Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Institut des Neurosciences Cliniques de Rennes (INCR)-CHU Pontchaillou [Rennes]-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Psychiatrie de l'adulte [Rennes], Centre Hospitalier Guillaume Régnier-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Rennes 1 (UR1), Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Developmental Brain and Behaviour Unit, University of Southampton, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, Université Paris Descartes - Paris 5 (UPD5), Groupement de recherche en Psychiatrie (GDR Psychiatrie (3557)), Centre National de la Recherche Scientifique (CNRS), 08-MNP-007, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Génome Québec, Canadian Foundation for Innovation, PIM2010ERM-00642, Ministry of Science and Innovation, New Zealand, Fundación Alicia Koplowitz, Université de Montréal, ERANET Neuron, Fondation Pierre Deniker, SAF2008-05674-C03-00, Ministerio de Educación y Ciencia, 2009SGR827, Comissionat per a Universitats i Recerca del DIUE, Genome Canada, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-Centre Hospitalier Guillaume Régnier, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université de Montréal-CHU de Montréal, Comportement et noyaux gris centraux [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université européenne de Bretagne ( UEB ) -CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université européenne de Bretagne ( UEB ) -Centre Hospitalier Guillaume Régnier, Laboratoire de neurosciences expérimentales et cliniques ( LNEC ), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of Southampton [Southampton], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Hôpital Sainte-Anne, Université Paris Descartes - Paris 5 ( UPD5 ), Groupement de recherche en Psychiatrie ( GDR Psychiatrie (3557) ), and Centre National de la Recherche Scientifique ( CNRS )
Subjects: Genotyping Techniques, [SDV]Life Sciences [q-bio], European Continental Ancestry Group, Biology, Polymorphism, Single Nucleotide, White People, Histone Deacetylases, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Genetic, Humans, Family, Genetic Predisposition to Disease, Epigenetics, Polymorphism, Biological Psychiatry, Exome sequencing, Genetic Association Studies, 030304 developmental biology, Genetic association, Genetics, 0303 health sciences, Multifactor dimensionality reduction, [ SDV ] Life Sciences [q-bio], HDAC11, Haplotype, Epistasis, Genetic, Single Nucleotide, Tag SNP, 3. Good health, Psychiatry and Mental health, Haplotypes, Mutation, Epistasis, Schizophrenia, Histone deacetylase, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND: Histone deacetylases (HDACs) are key enzymes of histone acetylation, and abnormalities in histone modifications and in the level of HDAC proteins have been reported in schizophrenia. The objective of the present study was to systematically test the HDAC genes for its association with schizophrenia. METHODS: A family-based genetic association study (951 Caucasian subjects in 313 nuclear families) using 601 tag-single nucleotide polymorphisms in HDAC genes was conducted followed by a replication study of top-ranked markers in a sample of 1427 Caucasian subjects from 241 multiplex families and 176 trios. Epistasis interaction was tested by using the pedigree-based generalized multifactor dimensionality reduction (GMDR). Furthermore, we analyzed exome sequencing data of 1134 subjects for detection of rare mutations in HDAC genomic regions. RESULTS: In the exploratory study, ten markers were in significant association with schizophrenia (P\textless0.01). One maker rs14251 (HDAC3) was replicated (P=0.04) and remained significant in the whole sample (P=0.004). GMDR identified that a significant three-locus interaction model was detected involving rs17265596 (HDAC9), rs7290710 (HDAC10) and rs7634112 (HDAC11) with a good testing accuracy (0.58). No rare mutations were found associated with schizophrenia. CONCLUSION: This first exploratory systematic study of the HDAC genes provides consistent support for the involvement of the HDAC3 gene in the etiology of schizophrenia. A statistical epistatic interaction between HDAC9, HDAC10, and HDAC11 was detected and seems biologically plausible
Published: 2014
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85. French adaptation of the Orientation To Happiness Scale and the impact of Quality of Life in French Students

Author: Martin-Krumm, Charles, Kern, Laurence, Fontayne, Paul, Romo, Lucia, Boudoukha, Abdel Halim, Boniwell, Ilona, Centre de Recherche sur l'Education, les apprentissages et la didactique (CREAD), Institut universitaire de formation des maîtres - Bretagne (IUFM Bretagne), Université de Brest (UBO)-Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre de Recherche sur le Sport et le Mouvement (CeRSM), Université Paris Nanterre (UPN), EA 4430, Clinique, Psychanalyse, Développement (CliPsyD), Université Paris Nanterre (UPN)-Université Paris Nanterre (UPN), Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Cognitions Humaine et ARTificielle (CHART), Université Paris 8 Vincennes-Saint-Denis (UP8)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Nanterre (UPN)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), EA 4638, Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Université de Nantes - UFR Lettres et Langages (UFRLL), École pratique des hautes études (EPHE)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Martin-Krumm, Charles, Centre de Recherche sur l'Education, les apprentissages et la didactique ( CREAD EA 3875 ), Université de Brest ( UBO ) -Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université de Lorraine ( UL ) -Université Paris Descartes - Paris 5 ( UPD5 ), Institut Formation Education Physique et Sportive Angers ( IFEPSA ), Université Catholique de l'Ouest, Centre de Recherche sur le Sport et le Mouvement ( CeRSM ), Université Paris Nanterre ( UPN ), Clinique, Psychanalyse, Développement ( CliPsyD ), Clinique des maladies mentales et de l'encéphale ( CMME - Service de psychiatrie ), Université Paris Descartes - Paris 5 ( UPD5 ) -Hôpital Sainte-Anne, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Laboratoire de Psychologie des Pays de la Loire ( LPLL ), Université d'Angers ( UA ) -Université de Nantes ( UN ), Cognitions Humaine et ARTificielle ( CHART ), Université Paris Nanterre ( UPN ) -Université Paris 8 Vincennes-Saint-Denis ( UP8 ) -École pratique des hautes études ( EPHE ), and Ecole Centrale Paris
Subjects: Santé, [SHS.EDU]Humanities and Social Sciences/Education, [SHS.EDU] Humanities and Social Sciences/Education, Happiness, Well-being, Satisfaction, [SHS.PSY]Humanities and Social Sciences/Psychology, [ SCCO.PSYC ] Cognitive science/Psychology, health, Emotion Cognition et Comportement, psychometric properties, bonheur, [SHS.PSY] Humanities and Social Sciences/Psychology, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Psychologie, Éducation, recherche
Abstract: International audience; Happiness is the current hot topic whether in television, press or research. For some, it is immeasurable; for others it is quantifiable and thus has numerous measurement tools. After having defined happiness, the aim of the four studies presented below is to propose a valid French adaptation of the three-dimensional Orientation To Happiness questionnaire (OTH; Peterson, Park, & Seligman, 2005). In Study 1, successive PCA and CFA revealed that there exists a three factor structure conforming to its theoretical framework. Study 2 was used to test different models to confirm this factor structure. We found two models that proved to be adequate. The results of Study 3 demonstrate satisfactory test-retest stability for each of the three subscales. Study 4 was undertaken to test the convergent validity of the scale. Moreover, this study showed the relationship between variables linked to quality of life and their impact on happiness. To summarize, the four studies together demonstrate satisfactory psychometric qualities of the scale that is now called "Échelle Francophone d'Inclinaison au Bonheur" (EFIB), and show how happiness is impacted by different variables linked to quality of life.
Published: 2014
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86. Limbic versus cognitive target for deep brain stimulation in treatment-resistant depression: accumbens more promising than caudate

Author: Florence Le Jeune, Bruno Aouizerate, Nematollah Jaafari, Gabriel Robert, Paul Sauleau, Marie-Odile Krebs, Stephan Chabardes, Julie Anne Peron, Mircea Polosan, Sophie Drapier, Marc Vérin, Jérôme Yelnik, Bruno Millet, Claire Haegelen, Bertrand Devaux, Philippe Cornu, Philippe Fossati, Thérèse M. Jay, Nicolas Baup, Florian Naudet, Jean Michel Reymann, Denys Fontaine, Dominique Drapier, Bruno Giordana, Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Institut des Neurosciences Cliniques de Rennes (INCR)-CHU Pontchaillou [Rennes]-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Psychiatrie de l'adulte [Rennes], Centre Hospitalier Guillaume Régnier-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Rennes 1 (UR1), Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, Hôpital Pasteur [Nice] (CHU), Service de neurochirurgie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [APHP], Hôpital Charles Perrens, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [Rennes], CHU Pontchaillou [Rennes], Université de Genève (UNIGE), Département de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Comportement et noyaux gris centraux [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université européenne de Bretagne ( UEB ) -CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université européenne de Bretagne ( UEB ) -Centre Hospitalier Guillaume Régnier, Laboratoire de neurosciences expérimentales et cliniques ( LNEC ), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Hôpital Sainte-Anne, Hôpital Pasteur [Nice] ( CHU ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université de Genève ( UNIGE ), CRLCC Eugène Marquis ( CRLCC ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-Centre Hospitalier Guillaume Régnier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier Charles Perrens [Bordeaux], Centre de Psychiatrie et Neurosciences (U894), Service de Neurologie [Rennes] = Neurology [Rennes], Université de Genève = University of Geneva (UNIGE), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR)
Subjects: Adult, Male, Cerebellum, Deep brain stimulation, medicine.medical_treatment, Caudate, [SDV]Life Sciences [q-bio], Clinical Neurology, Biophysics, Caudate nucleus, Stimulation, Neuropsychological Tests, Nucleus accumbens, Nucleus Accumbens, Cognition, Imaging, Three-Dimensional, ddc:150, Gyrus, medicine, Humans, Pharmacology (medical), Prospective Studies, Biological Psychiatry, Accumbens, Pharmacology, [ SDV ] Life Sciences [q-bio], Depression, Middle Aged, medicine.disease, Magnetic Resonance Imaging, ddc:128.37, Psychiatry and Mental health, medicine.anatomical_structure, Neurology, Frontal lobe, Positron-Emission Tomography, Anesthesia, Female, Neurology (clinical), Caudate Nucleus, Treatment-resistant depression, Psychology, Therapeutic trial, Follow-Up Studies
Abstract: International audience; High-frequency deep brain stimulation (DBS) represents a major stake for treatment for treatment-resistant depression (TRD). We describe a preliminary trial of DBS of two potential brain targets in chronic TRD: the nucleus accumbens (Acb) and, in the event of failure, the caudate nucleus. Patients were followed for 6 months before surgery (M0). From M1 to M5, they underwent stimulation of the Acb target. PET scans allowed us to track metabolic modifications resulting from this stimulation. The caudate target of nonresponders was stimulated between M5 and M9. Patients then entered an extension phase, in which it was possible to adapt stimulation parameters and treatments. Six patients were included and four were operated on. At M5, none of the patients were either responders or remitters, but we did observe a decrease in Hamilton Depression Rating Scale (HDRS) scores. Three patients were switched to caudate stimulation, but no improvement was observed. During the extension phase, the Acb target was stimulated for all patients, three of whom exhibited a significant response. A decrease in glucose metabolism was observed after Acb stimulation, in the posterior cingulate gyrus, left frontal lobe, superior and medial gyrus, and bilateral cerebellum. An increase in metabolism was observed in the bilateral frontal lobe (superior gyrus), left frontal lobe (medial gyrus), and right limbic lobe (anterior cingulate gyrus). The results of this trial suggest that Acb is a more promising target than the caudate. NCT01569711.
Published: 2014
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87. Ethanol and epigenetic : neuroplastic and functional consequences in mice

Author: Stragier, Emilien, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université René Descartes - Paris V, Laurence Lanfumey, Centre de Psychiatrie et Neurosciences (CPN - U894), and Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5)
Subjects: Souris, Capacités cognitives, Hippocampe, Plasticity, Neurogenesis, Épigénétique, TrkB, Hippocampus, Chronic ethanol intake, Mice, BDNF, Cognitive performances, Plasticité, Prise chronique d’éthanol, Epigenetics, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurogenèse
Abstract: Chronic and excessive ethanol consumption triggers neurobiological adaptations within the central nervous system, which are responsible for the development of an addiction. Ethanol induces adaptive mechanisms linked to epigenetic regulations leading to functional and structural changes, and also provokes a neurodegeneration responsible for the cognitive deficits observed in alcohol abusers. Among the different animal models available for studying the effects of chronic ethanol consumption, C57BL/6J mice are among the most relevant. These mice display high ethanol preference, making them a good model for studying the consequences of chronic and free-choice ethanol consumption. The purpose of this work was to study the links between epigenetic mechanisms and hippocampal neuroplasticity and to evaluate the behavioural consequences induced by chronic ethanol consumption in C57BL/6J mice. We showed that, in the hippocampus, chronic ethanol consumption induced global epigenetic modulations that were correlated with chromatin remodelling at the BDNF gene level. These effects involved post-translational histone modifications and DNA methylation. Epigenetic changes at the BDNF gene level probably allowed the increase in BDNF protein expression observed within the hippocampal dentate gyrus in mice having consumed ethanol for 3 weeks. Upregulation of BDNF expression was linked to both the stimulation of intracellular cascades downstream BDNF/TrkB receptor activation, and the increase in neurogenesis within the dentate gyrus. Using a specific TrkB receptor antagonist, ANA-12, we demonstrated that the hippocampal neurogenesis induced by chronic ethanol intake was under the control of BDNF. Behavioural analysis evidenced learning and memory impairments after ethanol consumption without synaptic plasticity alteration within the hippocampus, suggesting the involvement of other mechanisms in the cognitive deficits. Altogether, these data bring new elements for understanding the hippocampal neurogenesis stimulation observed under chronic and voluntary ethanol consumption in C57BL/6J mice. Moreover, this apparent increase in plasticity might probably be considered as an adaptive and compensatory mechanism in response to the cognitive deficits induced by ethanol consumption.; La consommation chronique et excessive d’éthanol provoque des modifications neurobiologiques adaptatives. Les mécanismes qui les contrôlent sont multiples et certains ont été reliés à des régulations épigénétiques conduisant à des modifications structurelles et fonctionnelles. L’éthanol induit également une neurodégénérescence de l’hippocampe responsable de déficits cognitifs. Parmi l’ensemble des modèles animaux qui sont utilisés pour étudier les effets d’une consommation chronique d’alcool, figurent les souris de la lignée C57BL/6J. Ces souris possèdent une appétence naturelle pour l’éthanol faisant d’elles un modèle de choix pour étudier les conséquences de la consommation chronique d’éthanol. Le but de ce travail de thèse a été d’étudier les relations entre les mécanismes épigénétiques et la modulation de la neuroplasticité de l’hippocampe à la suite d’une consommation chronique d’éthanol chez les souris C57BL/6J, et d’en évaluer les conséquences comportementales. Nous avons montré que la consommation chronique d’éthanol induit, au niveau de l’hippocampe, des modulations épigénétiques globales corrélées à un remodelage chromatinien au sein du gène du BDNF, impliquant à la fois les modifications post-traductionnelles des histones et la méthylation de l’ADN. Ces modifications épigénétiques sont certainement responsables de l’augmentation d’expression protéique du BDNF observée dans l’hippocampe, et plus particulièrement dans le gyrus denté, après 3 semaines de consommation chronique d’éthanol en libre choix. L’accroissement de l’expression du BDNF induit une stimulation des voies de la signalisation intracellulaire dépendantes de l’activation du récepteur TrkB du BDNF, et une augmentation de la neurogenèse du gyrus denté. Les effets de l’antagoniste spécifique du récepteur TrkB, ANA 12, démontrent que l’augmentation de la neurogenèse observée chez les souris C57BL/6J après la prise chronique d’éthanol, est sous le contrôle unique du complexe BDNF/TrkB. L’analyse comportementale des souris C57BL/6J ayant consommé de l’éthanol, montre une détérioration des capacités d’apprentissage et de mémoire sans modification de la plasticité synaptique dans l’hippocampe, suggérant ainsi que d’autres mécanismes sont impliqués dans ces déficits cognitifs. L’ensemble de ces données apporte de nouveaux éléments de compréhension concernant la stimulation de la neurogenèse hippocampique chez les souris C57BL/6J lors d’une consommation chronique en libre choix d’éthanol. Il est probable que cette apparente augmentation de plasticité soit un mécanisme adaptatif et compensatoire à la détérioration des fonctions cognitives induite par une consommation chronique d’alcool.
Published: 2014

88. SET translocation is associated with increase in caspase cleaved amyloid precursor protein in CA1 of Alzheimer and Down syndrome patients

Author: Patricia Facchinetti, Emilie Dorard, Bernadette Allinquant, Nicole Déglon, Marie-Claude Gaillard, Chantal Guihenneuc-Jouyaux, Emmanuel Brouillet, Vincent Contremoulins, Véronique Sazdovitch, Charles Duyckaerts, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie Environnementale : Impact Sanitaire des Pollutions (EA 4064), Université Paris Descartes - Paris 5 (UPD5), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire des Maladies Neurodégénératives - UMR 9199 ( LMN ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -CHU Pitié-Salpêtrière [APHP], Epidémiologie Environnementale : Impact Sanitaire des Pollutions ( EA 4064 ), Université Paris Descartes - Paris 5 ( UPD5 ), Centre de Psychiatrie et Neurosciences (U894), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Aging, Down syndrome, Cytoplasm, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hippocampus, Chromosomal translocation, tau Proteins, Amyloid beta-Protein Precursor, Mice, Alzheimer Disease, medicine, Amyloid precursor protein, Animals, Humans, Histone Chaperones, Phosphorylation, CA1 Region, Hippocampal, Caspase, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Aged, Aged, 80 and over, Neurons, biology, General Neuroscience, Dentate gyrus, Middle Aged, medicine.disease, Cell biology, DNA-Binding Proteins, Mice, Inbred C57BL, nervous system, Caspases, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Dentate Gyrus, biology.protein, Disease Progression, Female, Neurology (clinical), Geriatrics and Gerontology, Alzheimer's disease, Down Syndrome, Neuroscience, Developmental Biology, Transcription Factors
Abstract: International audience; Caspase cleaved amyloid precursor protein (APPcc) and SET are increased and mislocalized in the neuronal cytoplasm in Alzheimer Disease (AD) brains. Translocated SET to the cytoplasm can induce tau hyperphosphorylation. To elucidate the putative relationships between mislocalized APPcc and SET, we studied their level and distribution in the hippocampus of 5 controls, 3 Down syndrome and 10 Alzheimer patients. In Down syndrome and Alzheimer patients, APPcc and SET levels were increased in CA1 and the frequency of both localizations in the neuronal cytoplasm was high in CA1, and low in CA4. As the increase of APPcc is already present at early stages of AD, we overexpressed APPcc in CA1 and the dentate gyrus neurons of adult mice with a lentiviral construct. APPcc overexpression in CA1 and not in the dentate gyrus induced endogenous SET translocation and tau hyperphosphorylation. These data suggest that increase in APPcc in CA1 neurons could be an early event leading to the translocation of SET and the progression of AD through tau hyperphosphorylation.
Published: 2014
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89. Activité Physique, santé et ressources des étudiants : Habitudes de vie des étudiants de Nanterre

Author: Kern, L., Kotbagi, G., Morvan, Y., Boudoukha, AH., Martin-Krumm, C., Besançon, Maud, Fenouillet, Fabien, Rousseau, A., Muller, I., Fontayne, P., Riazuelo, H., Romo, L., Université Paris Nanterre (UPN), Clinique, Psychanalyse, Développement (CliPsyD), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cognitions Humaine et ARTificielle (Nanterre) (CHArt - Université Paris Nanterre), Cognitions Humaine et ARTificielle (CHART), Université Paris 8 Vincennes-Saint-Denis (UP8)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Nanterre (UPN)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Paris 8 Vincennes-Saint-Denis (UP8)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Nanterre (UPN)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), École pratique des hautes études (EPHE)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-École pratique des hautes études (EPHE)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), École pratique des hautes études (EPHE)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), HAL Nanterre, Administrateur, Université Paris Nanterre ( UPN ), Clinique, Psychanalyse, Développement ( CliPsyD ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cognitions Humaine et ARTificielle (Nanterre) ( CHArt - Université Paris Nanterre ), Cognitions Humaine et ARTificielle ( CHART ), Université Paris 8 Vincennes-Saint-Denis ( UP8 ) -École pratique des hautes études ( EPHE ) -Université Paris Nanterre ( UPN ) -Université Paris 8 Vincennes-Saint-Denis ( UP8 ) -École pratique des hautes études ( EPHE ) -Université Paris Nanterre ( UPN ), Université Paris 8 Vincennes-Saint-Denis ( UP8 ) -École pratique des hautes études ( EPHE ) -Université Paris Nanterre ( UPN ), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Paris Nanterre (UPN)-Université Paris 8 Vincennes-Saint-Denis (UP8)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Paris Nanterre (UPN)-Université Paris 8 Vincennes-Saint-Denis (UP8)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)
Subjects: [SHS.PSY] Humanities and Social Sciences/Psychology, [ SHS.PSY ] Humanities and Social Sciences/Psychology, [SHS.EDU]Humanities and Social Sciences/Education, [SHS.EDU] Humanities and Social Sciences/Education, [SHS.PSY]Humanities and Social Sciences/Psychology, [ SHS.EDU ] Humanities and Social Sciences/Education, Cognitions Humaine et Artificielle, ComputingMilieux_MISCELLANEOUS
Abstract: National audience; no abstract
Published: 2014

90. Neurodevelopmental and environmental hypotheses of negative symptoms of schizophrenia

Author: Frédéric Limosin, Centre de Psychiatrie et Neurosciences (CPN - U894), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5), Service de psychiatrie adulte et gériatrique, Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - Hôpitaux Universitaires Paris Ouest - Hôpital Corentin Celton [Issy-les-Moulineaux], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Corentin Celton [Issy-les-Moulineaux], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and BMC, Ed.
Subjects: Adult, Hypothalamo-Hypophyseal System, Alogia, Dopamine, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Pituitary-Adrenal System, Review, Disease, Environment, 03 medical and health sciences, Glutamatergic, 0302 clinical medicine, medicine, Humans, Tonic (music), Apathy, Child, Avolition, Maternal deprivation, Brain, medicine.disease, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Negative symptoms, Neurodevelopmental hypothesis, medicine.symptom, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract: International audience; The negative symptoms of schizophrenia, avolition, alogia, apathy and impaired or nonexistent social functioning, are strongly correlated with the progressive course and long-term prognosis of the disease, undermining the patient's ability to integrate socially, interpersonal skills and quality of life. At a time when new drug strategies are being developed, a better understanding of the etiology and pathogenesis underpinning the occurrence of negative symptoms constitutes an essential prerequisite for real therapeutic advances. Approaching this vulnerability from the neurodevelopmental perspective is especially pertinent with regard to the experimental studies conducted in animals. Several models have been put forward, involving a variety of topics such as the deleterious impact of a prenatal infection or of early maternal deprivation on brain development, or else the consequences of trauma and abuse suffered during childhood. These various models are based on biological abnormalities that could guide the identification of new therapeutic targets. They notably include the hyperreactivity of the hypothalamic-pituitary-adrenal axis and dysfunction of corticostriatal glutamatergic transmission. As such, in the traumagenic model, which associates neurodevelopmental and neurodegenerative processes, the dysfunction of corticostriatal glutamatergic transmission, by reducing the tonic dopamine release, could be the cause of an increase in the phasic dopamine release linked to stress. This excessive phasic response to stress may induce cerebral damage by increasing excitotoxicity and oxidative stress.
Published: 2014
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91. Les effets néfastes du cannabis, un facteur de risque à l'adolescence ?

Author: Dervaux, Alain, Morvan, Yannick, Laqueille, Xavier, Krebs, Marie-Odile, HAL Nanterre, Administrateur, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Clinique, Psychanalyse, Développement ( CliPsyD ), Université Paris Nanterre ( UPN ), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Hôpital Sainte-Anne, Université Paris Descartes - Paris 5 ( UPD5 ), Groupement de recherche en Psychiatrie ( GDR Psychiatrie (3557) ), Centre National de la Recherche Scientifique ( CNRS ), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique, Psychanalyse, Développement (CliPsyD), Université Paris Nanterre (UPN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, Université Paris Descartes - Paris 5 (UPD5), Groupement de recherche en Psychiatrie (GDR Psychiatrie (3557)), Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne
Subjects: alcool, L'addiction chez les adolescents jeux video, [SHS.PSY]Humanities and Social Sciences/Psychology, Fabien Gierski, Drogues et toxicomanie, Psychologie du développement, Marie Choquet, Nicole Battaglia, [SHS.PSY] Humanities and Social Sciences/Psychology, [ SHS.PSY ] Humanities and Social Sciences/Psychology, Psychologie-Psychanalyse, Collectif, drogues...de l'assuétude à l'addiction, Psychologie de l'adolescent
Abstract: à venir
Published: 2014

92. Subjects at Ultra High Risk for psychosis have 'heterogeneous' intellectual functioning profile: a multiple-case study

Author: M. Kazes, Marie-Odile Krebs, Charlotte Alexandre, Dominique Willard, Yannick Morvan, Raphaël Gaillard, Alice Rampazzo, Emilie Magaud, Université Paris Nanterre (UPN), Clinique, Psychanalyse, Développement (CliPsyD), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CNR, Istituto Sperimentale Talassografico, Contraintes mécaniques et tissu osseux, Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroimagerie cognitive (LCogn), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service hospitalo-universitaire de santé mentale et de thérapeutique, CHU Paris, Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Nanterre ( UPN ), Clinique, Psychanalyse, Développement ( CliPsyD ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Neuroimagerie cognitive ( LCogn ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Centre de Psychiatrie et Neurosciences (U894)
Subjects: Adult, Male, medicine.medical_specialty, Psychosis, Adolescent, Population, Intelligence, [ SCCO.PSYC ] Cognitive science/Psychology, Neuropsychological Tests, Young Adult, Borderline intellectual functioning, Risk Factors, medicine, Outpatient clinic, Humans, Psychiatry, education, Biological Psychiatry, Retrospective Studies, First episode, Psychiatric Status Rating Scales, education.field_of_study, Neuropsychology, Wechsler Scales, Wechsler Adult Intelligence Scale, Cognition, medicine.disease, 3. Good health, Psychiatry and Mental health, Psychotic Disorders, [SCCO.PSYC]Cognitive science/Psychology, Female, Psychology, Cognition Disorders
Abstract: International audience; In Ultra High Risk (UHR) studies, intellectual functioning is commonly assessed using premorbid IQ tools as a covariate. The aim of this study was to show that the use of the Wechsler Adult Intelligence Scale (WAIS) could yield accurate neuropsychological profiling and that an alternative approach such as a multiple-case study could be a more interesting way to isolate discrete cognitive processes in the early stage of illness.The studied population consisted of 198 adolescents and young adults (16–30 y.o.) referred to our outpatient clinic. After the CAARMS' interview, we defined 3 subgroups: UHR (N = 104), First Episode (FE; N = 30), and Help-Seekers (HS; N = 64) who were neither UHR nor psychotic. Intellectual functioning was assessed by the WAIS-III (9 subtests version) and ‘heterogeneous’ intellectual profiles were defined based on the existence of a 3-point difference in scoring at subtests constitutive of the same WAIS index.While UHR did not differ from FE or HS on WAIS' scores and sub-scores, the multiple-case study indicated a higher proportion of ‘heterogeneous’ profiles in the Verbal Comprehension Index in the UHR sample than in FE and HS (p = 0.04).The disease progression could heterogeneously impact on specific domains, in patterns depending on the stage of the illness. This approach exploring intra-subject WAIS performances might be more relevant than the use of global scores in detecting the subtle cognitive alteration of emerging psychosis.
Published: 2014
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93. The Wnt Receptor Ryk Reduces Neuronal and Cell Survival Capacity by Repressing FOXO Activity During the Early Phases of Mutant Huntingtin Pathogenicity

Author: Olivia L. Bordiuk, Nicolas Offner, Anne-Marie Orfila, Robert J. Ferrante, Rafael P. Vázquez-Manrique, Michael M. Halford, Jinho Kim, Christina K. Edgerly, Wange Lu, Cendrine Tourette, Karen M. Smith, Anne Louise, Sonia Hernandez, Kerry Cormier, Jean-Philippe Vert, Si Ho Choi, Jungmok Lyu, J. Alex Parker, Francesca Farina, Steven A. Stacker, Christian Neri, Sophie Menet, Jessica Voisin, Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Neurology [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), VA Bedford Geriatric Research Education and Clinical Center, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, Cytométrie (Plate-forme), Institut Pasteur [Paris], Centre de Bioinformatique (CBIO), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, University of California, Peter MacCallum Cancer Center, This work was supported by Inserm and Associated International Laboratory ‘Neuronal longevity’ (http://www.inserm.fr/), AP-HP (http://www.aphp.fr/), ‘‘Equipe FRM Ile-de-France’’ program of the Fondation pour la Recherche Me´dicale (http://www.frm.org/) Grant DEQ20061107955, the Agence Nationale de la Recherche (http://www.agence-nationale-recherche.fr/) Grants ANR-08-MNPS-024-01 and ANR-12-BSV4-0023-01 and the Association Franc¸aise contre les Myopathies (http://www.afm-telethon.fr/), Paris, France, and the Hereditary Disease Foundation (http://www.hdfoundation.org/home.php) and CHDI Foundation (http://chdifoundation.org/), USA. C.T. is supported by AP-HP under the University Hospital Department ‘Fight Aging and Stress’ program. J.A.P. was supported by a Young Researcher Award from Inserm. R.V. was supported by a Poste Vert fellowship from Inserm. J.V. is supported by the Association Huntington France. J.K. is supported by the Bumpus Foundation. This work was also supported by National Institutes of Health (http://www.nih.gov/) Grants NS045242, NS045806, NS058793, and NS066912, and by the Veterans Administration (http://www.va.gov/) (R.J.F.). The Cell Imaging and Flow Cytometry facility of the IFR 83 (Paris, France) is supported by the Conseil regional Ile-de-France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Brunet, Émilie, Institut Pasteur [Paris] (IP), Mines Paris - PSL (École nationale supérieure des mines de Paris), University of California (UC), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing ( B2A ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Charles Foix - Jean Rostand, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Charles Foix - Jean Rostand, University of Pittsburgh School of Medicine [Pittsburgh], Centre de Bioinformatique ( CBIO ), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University ( PSL ), Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE-MINES ParisTech - École nationale supérieure des mines de Paris-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Boston University School of Medicine, Centre de Psychiatrie et Neurosciences (U894), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Charles Foix - Jean Rostand, MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University (PSL), and MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)-MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Huntingtin, Mutant, Mice, Neurobiology of Disease and Regeneration, Medicine and Health Sciences, Amyloid precursor protein, Biology (General), [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Wnt Signaling Pathway, Oligonucleotide Array Sequence Analysis, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Neurons, Serotonin Plasma Membrane Transport Proteins, Genetics, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], biology, General Neuroscience, Wnt signaling pathway, Forkhead Transcription Factors, Animal Models, Transfection, Middle Aged, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Cell biology, Huntington Disease, Neurology, Female, General Agricultural and Biological Sciences, Research Article, Programmed cell death, Beta-catenin, QH301-705.5, Mice, Transgenic, Research and Analysis Methods, Neuroprotection, General Biochemistry, Genetics and Molecular Biology, Cell Line, Model Organisms, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], Presenilin-1, Animals, Humans, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Aged, General Immunology and Microbiology, Receptor Protein-Tyrosine Kinases, Biology and Life Sciences, nervous system, biology.protein, Receptors, Wnt, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Neuroscience
Abstract: A study of Huntington's disease reveals that neurons might fail to cope with maintaining their function during the pre-symptomatic, pathogenic phases of HD, possibly due to the early repression of key longevity-promoting transcription factors by abnormal developmental signaling., The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including γ-secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD). Although the Wnt pathway may be neuroprotective, the role of Ryk in neurodegenerative disease remains unknown. We found that Ryk is up-regulated in neurons expressing mutant huntingtin (HTT) in several models of Huntington's disease (HD). Further investigation in Caenorhabditis elegans and mouse striatal cell models of HD provided a model in which the early-stage increase of Ryk promotes neuronal dysfunction by repressing the neuroprotective activity of the longevity-promoting factor FOXO through a noncanonical mechanism that implicates the Ryk-ICD fragment and its binding to the FOXO co-factor β-catenin. The Ryk-ICD fragment suppressed neuroprotection by lin-18/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity, and abolished β-catenin protection of mutant htt striatal cells against cell death vulnerability. Additionally, Ryk-ICD was increased in the nucleus of mutant htt cells, and reducing γ-secretase PS1 levels compensated for the cytotoxicity of full-length Ryk in these cells. These findings reveal that the Ryk-ICD pathway may impair FOXO protective activity in mutant polyglutamine neurons, suggesting that neurons are unable to efficiently maintain function and resist disease from the earliest phases of the pathogenic process in HD., Author Summary Neuronal cell decline in neurodegenerative disease can be caused by inherited mutations and involves neuronal dysfunction followed by neuronal death. The ability of neurons to cope with the chronic stress induced by mutant protein expression may determine the course of their decline and eventual demise. Although the pathophysiological importance of these stress responses has been previously shown, very little is known about the signaling networks that regulate neuronal homeostasis during the early presymptomatic—but pathogenic—phases of a neurodegenerative disorder such as Huntington's disease (HD). In particular, it remains unclear whether neuronal differentiation factors regulate stress response pathways during neurodegenerative disease and how this might impact the overall capacity of neurons to cope with stress and maintain their function. Here, we show that the Wnt receptor Ryk, a protein known to be important for neurogenesis, is increased in different animal models of HD, before or during the early phases of the disease process. Interestingly, increased levels of Ryk repress activity of the FOXO proteins—a family of transcription factors that play a role in cell survival/longevity and in neuronal homeostasis and protection. Ryk represses FOXO protective activity, possibly directly, through its intracellular domain, a product of γ-secretase–mediated cleavage previously implicated in the birth of new cortical neurons. This highlights the regulation of HD neuron survival by a Ryk-dependent pathway that is distinct from canonical Wnt/Ryk signaling. From our findings, we postulate that neurons are unable to develop an efficient FOXO-mediated survival response during the very early, pathogenic phases of HD.
Published: 2014
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94. Psychotomimetic effects at initiation of cannabis use are associated with cannabinoid receptor 1 (CNR1) variants in healthy students

Author: Yannick Morvan, Raphaël Gaillard, Thérèse M. Jay, Oussama Kebir, Marie-Odile Krebs, Université Paris Nanterre (UPN), Clinique, Psychanalyse, Développement (CliPsyD), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroimagerie cognitive (LCogn), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service hospitalo-universitaire de santé mentale et de thérapeutique, CHU Paris, Université Paris Nanterre ( UPN ), Clinique, Psychanalyse, Développement ( CliPsyD ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Neuroimagerie cognitive ( LCogn ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Centre de Psychiatrie et Neurosciences (U894)
Subjects: Male, medicine.medical_specialty, Psychosis, Adolescent, Genotype, medicine.medical_treatment, Marijuana Smoking, [ SCCO.PSYC ] Cognitive science/Psychology, Bioinformatics, Euphoriant, Young Adult, Cellular and Molecular Neuroscience, Gene Frequency, Receptor, Cannabinoid, CB1, Neurotrophic factors, Surveys and Questionnaires, medicine, Humans, RNA, Messenger, Young adult, Psychiatry, Molecular Biology, Genetic Association Studies, Polymorphism, Single-Stranded Conformational, Cannabis, biology, Psychotomimetic, biology.organism_classification, medicine.disease, 3. Good health, Psychiatry and Mental health, [SCCO.PSYC]Cognitive science/Psychology, Hallucinogens, Regression Analysis, Anxiety, Female, Cannabinoid, medicine.symptom, Psychology, medicine.drug
Abstract: International audience; Cannabis induces a diverse range of subjective experiences including relaxation, anxiety, euphoria, sadness, cognitive difficulties and psychotic-like symptoms. In addition, although cannabis use is associated with an overall twofold increased risk of subsequent psychotic disorders, all individuals are not at equal risk of developing psychosis when exposed to cannabis. Inconsistent results have been reported regarding the influence of variants in the catechol-O-methyltransferase (COMT) gene2,3 or in other genes of interest, such as brain-derived neurotrophic factor (BDNF), cannabinoid receptor 1 (CNR1)4,5 and more convincingly, v-Akt murine thymoma viral oncogene homolog 1 (AKT1). Inter-individual variability in subjective experience is already present at initiation of cannabis use and could reflect intrinsic personal characteristics.
Published: 2014
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95. Brain Activity and Functional Coupling Changes Associated with Self-Reference Effect during Both Encoding and Retrieval

Author: Francis Eustache, Malo Gaubert, Pascale Piolino, Nicolas Villain, Nastassja Morel, Géraldine Rauchs, Béatrice Desgranges, Brigitte Landeau, Gaël Chételat, Florence Mézenge, Neuropsychologie cognitive et neuroanatomie fonctionnelles de la mémoire humaine, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Mémoire et Cognition, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the Fondation Plan Alzheimer (Alzheimer Plan 2008-2012), Agence Nationale de la Recherche (ANR LONGVIE 2007), Re'gion Basse Normandie, Institut National de la Sante' et de la Recherche Me'dicale (Inserm) and Ministe're de l'Enseignement Supe'rieur de la Recherche. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Eustache, Francis, École pratique des hautes études ( EPHE ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Adult, Male, Cingulate cortex, Neural Networks, Brain activity and meditation, Cognitive Neuroscience, Science, Neuroimaging, Social and Behavioral Sciences, Brain mapping, Young Adult, Learning and Memory, Memory, medicine, Psychology, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Working Memory, Prefrontal cortex, Biology, Episodic memory, Self-reference effect, Brain Mapping, Multidisciplinary, medicine.diagnostic_test, Cognitive Neurology, fMRI, Cognitive Psychology, Brain, Magnetic Resonance Imaging, Neurology, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Posterior cingulate, Mental Recall, Medicine, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Functional magnetic resonance imaging, Neuroscience, Research Article
Abstract: International audience; Information that is processed with reference to oneself, i.e. Self-Referential Processing (SRP), is generally associated with better remembering compared to information processed in a condition not related to oneself. This positive effect of the self on subsequent memory performance is called as Self-Reference Effect (SRE). The neural basis of SRE is still poorly understood. The main goal of the present work was thus to highlight brain changes associated with SRE in terms of activity and functional coupling and during both encoding and retrieval so as to assess the relative contribution of both processes to SRE. For this purpose, we used an fMRI event-related self-referential paradigm in 30 healthy young subjects and measured brain activity during both encoding and retrieval of self-relevant information compared to a semantic control condition. We found that SRE was associated with brain changes during the encoding phase only, including both greater activity in the medial prefrontal cortex and hippocampus, and greater functional coupling between these brain regions and the posterior cingulate cortex. These findings highlight the contribution of brain regions involved in both SRP and episodic memory and the relevance of the communication between these regions during the encoding process as the neural substrates of SRE. This is consistent with the idea that SRE reflects a positive effect of the reactivation of self-related memories on the encoding of new information in episodic memory.
Published: 2014
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96. Distorsions cognitives des joueurs de jeux de hasard et d'argent hors ligne et mixtes

Author: Kern , Laurence, Romo , Lucia, Kotbagi , Gayatri, Rémond , Jean-Jacques, Gorwood , Philip, Centre de Recherche sur le Sport et le Mouvement ( CeRSM ), Université Paris Nanterre ( UPN ), EA 4430, Clinique, Psychanalyse, Développement ( CliPsyD ), Université Paris Nanterre ( UPN ) -Université Paris Nanterre ( UPN ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Clinique des maladies mentales et de l'encéphale ( CMME - Service de psychiatrie ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Hôpital Sainte-Anne
Subjects: [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, [ SCCO.PSYC ] Cognitive science/Psychology, Emotion Cognition et Comportement
Abstract: National audience; à venir
Published: 2014

97. Episodic future thinking in semantic dementia : a cognitive and fMRI study

Author: Francis Eustache, Serge Belliard, Armelle Viard, Pascale Piolino, Vincent de la Sayette, Béatrice Desgranges, Eustache, Francis, Neuropsychologie cognitive et neuroanatomie fonctionnelles de la mémoire humaine, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Mémoire et Cognition, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], This work was supported by the University Hospital Center of Caen, Ecole Pratique de Hautes Etudes ( EPHE ) , Fondation pour l a Recherche sur le Cerveau ( FRC ) , Inserm, UCBN ( research unit U1077 ) ., École pratique des hautes études ( EPHE ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Male, hippocampus, lcsh:Medicine, Audiology, Thinking, Cognition, Medicine and Health Sciences, Image Processing, Computer-Assisted, Semantic memory, lcsh:Science, Prefrontal cortex, Brain Mapping, prefrontal cortex, Multidisciplinary, fMRI, Middle Aged, Magnetic Resonance Imaging, Frontal Lobe, medicine.anatomical_structure, Neurology, Frontal lobe, Frontotemporal Dementia, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, Research Article, medicine.medical_specialty, Semantic dementia, Neuroimaging, episodic future thinking, Atrophy, Memory, Mental Health and Psychiatry, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, Recall, Autobiographical memory, lcsh:R, Biology and Life Sciences, Medial frontal gyrus, medicine.disease, semantic dementia, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Mental Recall, Cognitive Science, Dementia, lcsh:Q, Neuroscience
Abstract: International audience; Semantic dementia (SD) is characterized by gradual loss of semantic memory. While episodic autobiographical memory seems relatively preserved, behavioral studies suggest that episodic future thinking is impaired. We used fMRI to measure brain activity in four SD patients (JPL, EP, LL, EG) while they envisioned future events and remembered personal past events. Twelve healthy elders served as controls. Episodic quality, emotion, mental imagery and level of consciousness (via remember/know judgements) were checked at debriefing. We analyzed the future compared to the past for each patient. All patients presented lateral temporal atrophy, but varied in terms of frontal and anterior hippocampal atrophy. Patient JPL presented atrophy in bilateral superior medial frontal gyri and left anterior hippocampus and was unable to engage in episodic future thinking, despite hyperactivations in frontal and occipital regions. Patient EP presented no atrophy in the anterior hippocampus, but atrophy in bilateral superior medial frontal gyrus and had difficulties to engage in episodic future thinking. Patient LL presented atrophy in left anterior hippocampus, but hyperactivated its right counterpart for future compared to past thinking, permitting her to project efficiently in the future in an episodic way. Patient EG presented no atrophy in the superior medial frontal gyri or anterior hippocampi and was able to engage in episodic future thinking. Altogether, patients' future projections differed depending on the severity and localization of their atrophy. The functional integrity of bilateral superior medial frontal gyri and anterior hippocampus appear crucial for episodic future thinking: atrophy of both structures strongly impairs future projection, while integrity of these structures or hyperactivation of residual tissue normalizes episodic future projection.
Published: 2014

98. Multilevel modelling of survey data: impact of the 2-level weights used in the pseudolikelihood

Author: Lucas, Jean-Paul, Sébille, Véronique, Le Tertre, Alain, Le Strat, Yann, Bellanger, Lise, Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé, PRES Université Nantes Angers Le Mans (UNAM), Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Université de Nantes (UN), National Institute of Public Health Surveillance, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Mathématiques Jean Leray (LMJL), Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), PRES Université Nantes Angers Le Mans ( UNAM ), Université de Nantes ( UN ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Laboratoire de Mathématiques Jean Leray ( LMJL ), and Université de Nantes ( UN ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: [ SDE ] Environmental Sciences, level-2 weights, multilevel model, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], [SDE]Environmental Sciences, public database, [ MATH.MATH-ST ] Mathematics [math]/Statistics [math.ST], [STAT.TH]Statistics [stat]/Statistics Theory [stat.TH], pseudolikelihood, [ STAT.TH ] Statistics [stat]/Statistics Theory [stat.TH], lead exposure data, survey data
Abstract: International audience; Approaches that use the pseudolikelihood to perform multilevel modelling on survey data have been presented in the literature.To avoid biased estimates due to unequal selection probabilities, conditional weights can be introduced at each level. Less-biased estimators can also be obtained in a two-level linear model if the level-1 weights are scaled. In this paper, we studied several level-2 weights that can be introduced into the pseudolikelihood when the sampling design and the hierarchical structure of the multilevel model do not match. Two-level and three-level models were studied. The present work was motivated by a study that aims to estimate the contributions of lead sources to polluting the interior floor dust of the rooms within dwellings. We performed a simulation study using the real data collected from a French survey to achieve our objective.We conclude that it is preferable to use unweighted analyses or, at the most, to use conditional level-2 weights in a two-level or a three-level model.We state some warnings and make some recommendations.
Published: 2014
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99. Méthylations de l'histone H3 et contrôle épigénétique des propriétés des cellules souches de gliomes

Author: Bogeas, Alexandra, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université René Descartes - Paris V, Hervé Chneiweiss, Centre de Psychiatrie et Neurosciences (CPN - U894), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5), and Centre de Psychiatrie et Neurosciences (U894)
Subjects: ChIP-seq, endocrine system, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, animal structures, H3K27me3, embryonic structures, Glioma stem cells, H3K4me3, Cellules souches de gliomes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Gliomas, the most frequent primary brain tumors, are resistant to current therapies and the survival rate of patients is very low. Within high-grade gliomas, a cell sub-population bearing stem-like properties has been isolated. These cells, called glioma stem cell (GSC), are capable of generating all glioma cellular sub-types. Recent data indicates that resistance of these aggressive tumors to therapies is mostly due to GSCs. Thus, targeting the GSCs and their stem-like properties is imperative in order to improve current therapies. [...] Another effective solution to treat GSCs is to force them to lose their stem-like properties. In this context, the aims of my major project were to characterize the epigenetic modifications of histone marks accompanying the loss of GSC stem-like properties under the influence of a cluster of micro-RNA, miR-302-367. GSCs are endowed with an exceptional plasticity, allowing them to gain or lose their stem-like state in response to modifications in their micro-environment. Our results identified the implication of miR-302-367 in the regulation of GSC plasticity. Its stable expression using lentivirus inhibits in an irreversible manner the stem-like and tumorigenic properties of GSC. The tumor-suppressor effect of this miR offers the possibility to decipher the mechanisms responsible for the maintenance or the loss of GSC stem-like properties. Using the model of GSC and their counterparts, GSC-miR-302-367, who lost their stem-like and tumorigenic properties, my aim was to identify the methylation status of histone H3 of the histone code which is known to be associated either to an active or to a repressive gene transcription. I focused on the trimethylation of lysine 4 (H3K4me3) and lysine 27 (H3K27me3), which are associated with an activation or repression of gene transcription, respectively. We performed a ChIP-seq (Chromatin-immunoprecipitation-sequencing) analysis of the respective associated genes followed by a transcriptomic (exon-array) analysis of both cell lines. Our results show that miR-302-367 expression does not alter in a global manner the expression levels of H3K4me3 and H3K27me3. On the contrary, we were able to detect modifications in a discrete group of genes. At least for the studied marks, the positive correlation between the identified histone marks and the gene expression levels indicates that the histone code is well preserved in cancer. GO (Gene Ontology) analysis indicates that miR-302-367-induced loss of stem-like properties is accompanied with activation of the differentiation process in GSC. Genes implicated in the regulation of stem-like and tumorigenic properties were found to bear the repressive histone mark in GSC-miR-302-367. From our analysis of the group of genes bearing the active histone mark in GSC and the repressive one in GSC-miR-302-367, emerged a network of transcription factors that could possibly participate in the regulation of GSC stem-like properties. Down-regulation using siRNA of a member of this network, namely ARNT2, highlighted its role in the maintenance of the proliferative dynamic, as well as the expression of the transcription factor Nanog (a major regulator of GSC stem-like properties), in GSC derived from distinct gliomas. Our histone mark modification analysis, not only elucidated the molecular pathways implicated in the maintenance or, on the contrary, in the loss of GSC stem-like properties, but also, highlighted the implication of new actors in these processes. The activator effect of ARNT2 on GSC proliferation, as well as on the expression of Nanog, observed in GSC bearing distinct genetic alterations and derived from different glioma, indicates that this transcription factor plays a major role, not documented thus far, in the regulation of GSC stem-like properties.; Les gliomes sont les tumeurs primitives les plus fréquentes du cerveau et restent de mauvais pronostic en raison de l’inefficacité des traitements actuels. Des cellules souches cancéreuses ont été isolées à partir de gliomes de haut grade de l’adulte. Ces cellules souches de gliomes (GSC) peuvent fournir tous les sous-types cellulaires qui composent la tumeur. De nombreuses données indiquent que la résistance aux traitements est due en grande partie aux GSC. Cibler les GSC et leurs propriétés souches constitue donc un enjeu thérapeutique important. [...] Une solution pertinente de ciblage thérapeutique est de forcer les GSC à quitter leur état souche. Dans ce cadre, mes principaux travaux ont eu pour but de caractériser les changements épigénétiques des marques d’histones qui accompagnent la répression des propriétés des GSC par un groupe de micro-ARN, miR-302-367. [...] L’étude de cette plasticité par notre équipe a abouti à l’identification de miR-302-367. Son expression forcée, à l’aide de lentivirus, bloque de façon irréversible les propriétés souches et initiatrices de tumeur des GSC. L’effet suppresseur de tumeur exercé par miR offre la possibilité d’identifier les mécanismes qui régulent le maintien ou la perte des propriétés des GSC. A l’aide d’un modèle formé par une lignée de GSC et de sa contrepartie dépourvue des propriétés souches et tumorigènes GSC-miR-302-367, je me suis attachée à caractériser les méthylations de l’histone H3, qui font parties du code d’histone associé à une transcription génique respectivement active ou réprimée. Je me suis axée sur la triméthylation de la lysine 4 (H3K4me3) et de la lysine 27 (H3K27me3), respectivement permissive et répressive de la transcription. Une analyse par ChIP-seq (Immunoprécipitation de la chromatine-séquençage) des gènes associés à ces marques a été associée à la caractérisation des transcriptomes des cellules par exon-array. Nos résultats montrent que l’expression du groupe de miR-302-367 ne modifie pas de façon globale les taux des marques H3K4me3 et H3K27me3. Par contre, des changements dans des groupes de gènes circonscrits ont pu être identifiés. La corrélation positive observée entre les marques d’histones et les taux d’expression des gènes montre une conservation du code d’histone dans les cellules cancéreuses, au moins pour les marques étudiées. L’analyse des termes GO (Gene Ontology) indique que la perte des propriétés induites par miR-302-367 s’accompagne d’un engagement de GSC dans une voie de différenciation. Les gènes portant la marque répressive dans les GSC-miR-302-367 participent notamment à des catégories fonctionnelles associées à l’expression de propriétés souches et tumorigènes. L’analyse du groupe de gènes portant une marque permissive dans les GSC et répressive dans les GSC-miR-302-367, a révélé un réseau de facteurs de transcription susceptible de participer au contrôle des propriétés souches des GSC. La répression à l’aide de siRNA d’un des membres de ce réseau, le facteur de transcription ARNT2, nous a permis de révéler son rôle dans le maintien des capacités prolifératives des GSC issues de gliomes distincts et dans l’expression du facteur de transcription Nanog, connu pour son rôle central dans le contrôle des propriétés souches des GSC. Nos résultats montrent que l’analyse des changements de marques d’histone offre donc non seulement une vue d’ensemble des différents réseaux moléculaires associés au maintien ou au contraire à la répression des propriétés des GSC, mais permet d’identifier de nouveaux acteurs. L’effet stimulateur d’ARNT2 sur la croissance cellulaire et l’expression de Nanog, dans des GSC dérivées de gliomes différents aux altérations génomiques distinctes, indique que ce facteur de transcription tient une place centrale, insoupçonnée jusqu’à présent, dans la hiérarchie des gènes qui gouvernent les propriétés des GSC.
Published: 2013

100. Spinal Cord Transection-Induced Allodynia in Rats - Behavioral, Physiopathological and Pharmacological Characterization

Author: Caroline Chevarin, Sandrine Barthélémy, Michel Hamon, Sylvie Bourgoin, Saïd M'Dahoma, Didier Orsal, Valérie Kayser, Farah Chali, Neuropsychopharmacologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurobiologie des signaux intercellulaires (NSI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Psychiatrie et Neurosciences (U894), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), HAL UPMC, Gestionnaire, Unité de Neuropsychopharmacologie [CHU Pitié-Salpétriêre], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Laboratoire de neurobiologie des signaux intercellulaires, CNRS UMR 7101, and Université Pierre et Marie Curie - Paris 6 ( UPMC )
Subjects: Male, Hot Temperature, Physiology, Pregabalin, lcsh:Medicine, Nervous System, Rats, Sprague-Dawley, Ganglia, Spinal, Medicine and Health Sciences, Medicine, lcsh:Science, Spinal cord injury, Pain Measurement, Mammals, Multidisciplinary, Morphine, Reverse Transcriptase Polymerase Chain Reaction, Animal Models, Tapentadol, Allodynia, medicine.anatomical_structure, Spinal Cord, Neurology, Hyperalgesia, Anesthesia, Vertebrates, Neuropathic pain, Cytokines, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Ketamine, Anatomy, medicine.symptom, Research Article, Nervous System Physiology, medicine.drug, Astrocyte, Gabapentin, Pain, Nerve Tissue Proteins, Research and Analysis Methods, Real-Time Polymerase Chain Reaction, Rodents, Model Organisms, Phenols, Pain Management, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Spinal Cord Injuries, Analysis of Variance, Activating Transcription Factor 3, business.industry, lcsh:R, Organisms, Biology and Life Sciences, Correction, Spinal cord, medicine.disease, Rats, Neuroanatomy, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Q, business, Neuroscience
Abstract: International audience; In humans, spinal cord lesions induce not only major motor and neurovegetative deficits but also severe neuropathic pain which is mostly resistant to classical analgesics. Better treatments can be expected from precise characterization of underlying physiopathological mechanisms. This led us to thoroughly investigate (i) mechanical and thermal sensory alterations, (ii) responses to acute treatments with drugs having patent or potential anti-allodynic properties and (iii) the spinal/ganglion expression of transcripts encoding markers of neuronal injury, microglia and astrocyte activation in rats that underwent complete spinal cord transection (SCT). SCT was performed at thoracic T8–T9 level under deep isoflurane anaesthesia, and SCT rats were examined for up to two months post surgery. SCT induced a marked hyper-reflexia at hindpaws and strong mechanical and cold allodynia in a limited (6 cm 2) cutaneous territory just rostral to the lesion site. At this level, pressure threshold value to trigger nocifensive reactions to locally applied von Frey filaments was 100-fold lower in SCT-versus sham-operated rats. A marked up-regulation of mRNAs encoding ATF3 (neuronal injury) and glial activation markers (OX-42, GFAP, P264, P267, TLR4) was observed in spinal cord and/or dorsal root ganglia at T6-T11 levels from day 2 up to day 60 post surgery. Transcripts encoding the proinflammatory cytokines IL-1b, IL-6 and TNF-a were also markedly but differentially up-regulated at T6–T11 levels in SCT rats. Acute treatment with ketamine (50 mg/kg i.p.), morphine (3–10 mg/ kg s.c.) and tapentadol (10–20 mg/kg i.p.) significantly increased pressure threshold to trigger nocifensive reaction in the von Frey filaments test, whereas amitriptyline, pregabalin, gabapentin and clonazepam were ineffective. Because all SCT rats developed long lasting, reproducible and stable allodynia, which could be alleviated by drugs effective in humans, thoracic cord transection might be a reliable model for testing innovative therapies aimed at reducing spinal cord lesion-induced central neuropathic pain.
Published: 2013
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