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1. βAPP Processing Drives Gradual Tau Pathology in an Age-Dependent Amyloid Rat Model of Alzheimer’s Disease

Author: Jérôme Braudeau, Nicola Salvatore Orefice, François Becher, Charlène Joséphine, Mickael Audrain, Benoit Souchet, Alexis Haddjeri, Yvette Akwa, Alexis-Pierre Bemelmans, Sandro Alves, Nathalie Cartier, Jean-Marie Billard, Thierry Delzescaux, Arthur Viode, Patrick Dutar, Brigitte Potier, Philippe Hantraye, Satoru Tada, Romain Fol, Nicole Déglon, 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, Laboratoire d'Etude du Métabolisme des Médicaments (LEMM), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Sorbonne Paris Cité (USPC), 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), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), 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), 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), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-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), 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), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut d'Imagerie BioMédicale (I2BM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, 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), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), 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), 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), and Centre de Psychiatrie et Neurosciences (U894)
Subjects: Male, 0301 basic medicine, Amyloid, Cognitive Neuroscience, Transgene, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Genetic Vectors, Long-Term Potentiation, Hippocampus, Plaque, Amyloid, tau Proteins, Inflammation, Disease, Protein aggregation, Protein Aggregation, Pathological, Amyloid beta-Protein Precursor, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Alzheimer Disease, mental disorders, Presenilin-1, medicine, Animals, Humans, Rats, Wistar, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Amyloid beta-Peptides, business.industry, Long-term potentiation, medicine.disease, Peptide Fragments, Disease Models, Animal, 030104 developmental biology, Disease Progression, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Tauopathy, medicine.symptom, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: The treatment of Alzheimer's disease (AD) remains challenging and requires a better in depth understanding of AD progression. Particularly, the link between amyloid protein precursor (APP) processing and Tau pathology development remains poorly understood. Growing evidences suggest that APP processing and amyloid-β (Aβ) release are upstream of Tau pathology but the lack of animal models mimicking the slow progression of human AD raised questions around this mechanism. Here, we described that an AD-like βAPP processing in adults wild-type rats, yielding to human APP, βCTF and Aβ levels similar to those observed in AD patients, is sufficient to trigger gradual Tauopathy. The Tau hyperphosphorylation begins several months before the formation of both amyloid plaques and tangle-like aggregates in aged rats and without associated inflammation. Based on a longitudinal characterization over 30 months, we showed that extrasynaptic and emotional impairments appear before long-term potentiation deficits and memory decline and so before Aβ and Tau aggregations. These compelling data allowed us to (1) experimentally confirm the causal relationship between βAPP processing and Tau pathology in vivo and without Tau transgene overexpression, (2) support the amyloidogenic cascade and (3) propose a 4-step hypothesis of prodromal AD progression.
Published: 2018
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2. Loss-of-function mutations in KIF14 cause severe microcephaly and kidney development defects in humans and zebrafish

Author: Daniel Pouly, Laurence Loeuillet, Joelle Roume, Xianghong Shan, Sophie Saunier, Alexandre Benmerah, Marion Failler, Marijn Stokman, Brigitte Leroy, Jelena Martinovic, Mohammadjavad Paydar, Isabel Filges, Virginie Magry, Marine Alves, Cheryl Y. Gregory-Evans, Benjamin H. Kwok, Marion Delous, John S. Allingham, Madeline Louise Reilly, Julia Tantau, Jacqueline R. Hellinga, Rachel H. Giles, Cécile Jeanpierre, Laboratoire des Maladies Rénales Héréditaires, Imagine - Institut des maladies génétiques (IMAGINE - U1163), 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), Université Paris Diderot - Paris 7 (UPD7), Utrecht University [Utrecht], Institut de Recherche en Immunologie et en Cancérologie [UdeM-Montréal] (IRIC), Université de Montréal (UdeM), Queen's University [Kingston, Canada], Service de foetopathologie [Béclère], Université Paris-Sud - Paris 11 (UP11)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Laboratoire Histologie Embryologie Cytogénétique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anatomie et de Cytologie Pathologiques [Poissy], CHI Poissy-Saint-Germain, Service de génétique [Poissy], University of British Columbia (UBC), University of Basel (Unibas), University Medical Center [Utrecht], This work was supported by the Fondation pour la Recherche Médicale (DEQ20130326532 to SS), the European Union’sSeventh Framework Programme (FP7/2007–2013) grant 305608 (EURenOmics, CJ), the GIS-Institut desMaladies Rares (AMA11025KSA to CJ and SS), the CIHR, NSERC, CCSRI, and FRQS (BK), the SwissNational Science Foundation (SNSF, IF), the Dutch Kidney Foundation KOUNCIL consortium(CP11.18). The Imagine Institute is supported by an ANR grant (ANR-A0-IAHU-01)., European Project: 305608,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,EURENOMICS(2012), Université Paris-Sud - Paris 11 (UP11)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Benmerah, Alexandre, and European Consortium for High-Throughput Research in Rare Kidney Diseases - EURENOMICS - - EC:FP7:HEALTH2012-10-01 - 2017-09-30 - 305608 - VALID
Subjects: 0301 basic medicine, Male, Microcephaly, Fluorescent Antibody Technique, Kinesins, [SDV.GEN] Life Sciences [q-bio]/Genetics, Kidney, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Ciliopathies, 0302 clinical medicine, Loss of Function Mutation, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Zebrafish, Genetics (clinical), Oncogene Proteins, biology, Cilium, General Medicine, Cell biology, Pedigree, Midbody, Phenotype, Female, Kidney Diseases, General Article, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Congenital Abnormalities, 03 medical and health sciences, Structure-Activity Relationship, Ciliogenesis, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Genetics, medicine, Animals, Humans, Genetic Predisposition to Disease, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, Genetic Association Studies, Cytokinesis, [SDV.GEN]Life Sciences [q-bio]/Genetics, Kidney metabolism, medicine.disease, biology.organism_classification, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Disease Models, Animal, 030104 developmental biology, Genetic Loci, Genes, Lethal, 030217 neurology & neurosurgery
Abstract: International audience; Mutations in KIF14 have previously been associated with either severe, isolated or syndromic microcephaly with renal hypodysplasia (RHD). Syndromic microcephaly-RHD was strongly reminiscent of clinical ciliopathies, relating to defects of the primary cilium, a signalling organelle present on the surface of many quiescent cells. KIF14 encodes a mitotic kinesin, which plays a key role at the midbody during cytokinesis and has not previously been shown to be involved in cilia-related functions. Here, we analysed four families with fetuses presenting with the syndromic form and harbouring biallelic variants in KIF14. Our functional analyses showed that the identified variants severely impact the activity of KIF14 and likely correspond to loss-of-function mutations. Analysis in human fetal tissues further revealed the accumulation of KIF14-positive midbody remnants in the lumen of ureteric bud tips indicating a shared function of KIF14 during brain and kidney development. Subsequently, analysis of a kif14 mutant zebrafish line showed a conserved role for this mitotic kinesin. Interestingly, ciliopathy-associated phenotypes were also present in mutant embryos, supporting a potential direct or indirect role for KIF14 at cilia. However, our in vitro and in vivo analyses did not provide evidence of a direct role for KIF14 in ciliogenesis and suggested that loss of kif14 causes ciliopathy-like phenotypes through an accumulation of mitotic cells in ciliated tissues. Altogether, our results demonstrate that KIF14 mutations result in a severe syndrome associating microcephaly and RHD through its conserved function in cytokinesis during kidney and brain development.
Published: 2018
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3. Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP)

Author: Violaine Planté-Bordeneuve, T. Lalu, Cécile Zaros, A. Ferreira, Catherine Lacroix, David H. Adams, Gérard Said, Planté-Bordeneuve, Violaine, Stéroides et système nerveux : physiopathologie moléculaire et clinique, and Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Chronic inflammatory demyelinating polyneuropathy, 030204 cardiovascular system & hematology, Gastroenterology, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Prealbumin, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, Amyloid Neuropathies, Familial, Nerve biopsy, biology, medicine.diagnostic_test, business.industry, Dysautonomia, Sensory loss, Middle Aged, Familial amyloid neuropathy, medicine.disease, 3. Good health, Surgery, Transthyretin, Amyloid Neuropathy, Molecular Diagnostic Techniques, biology.protein, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), medicine.symptom, business, Polyneuropathy, 030217 neurology & neurosurgery, Demyelinating Diseases
Abstract: International audience; Transthyretin familial amyloid polyneuropathies (TTR-FAPs) are autosomal dominant neuropathies of fatal outcome within 10 years after inaugural symptoms. Late diagnosis in patients who present as nonfamilial cases delays adequate management and genetic counseling. Clinical data of the 90 patients who presented as nonfamilial cases of the 300 patients of our cohort of patients with TTR-FAP were reviewed. They were 21 women and 69 men with a mean age at onset of 61 (extremes: 38 to 78 years) and 17 different mutations of the TTR gene including Val30Met (38 cases), Ser77Tyr (16 cases), Ile107Val (15 cases), and Ser77Phe (5 cases). Initial manifestations included mainly limb paresthesias (49 patients) or pain (17 patients). Walking difficulty and weakness (five patients) and cardiac or gastrointestinal manifestations (five patients), were less common at onset. Mean interval to diagnosis was 4 years (range 1 to 10 years); 18 cases were mistaken for chronic inflammatory demyelinating polyneuropathy, which was the most common diagnostic error. At referral a length-dependent sensory loss affected the lower limbs in 2, all four limbs in 20, and four limbs and anterior trunk in 77 patients. All sensations were affected in 60 patients (67%), while small fiber dysfunction predominated in the others. Severe dysautonomia affected 80 patients (90%), with postural hypotension in 52, gastrointestinal dysfunction in 50, impotence in 58 of 69 men, and sphincter disturbance in 31. Twelve patients required a cardiac pacemaker. Nerve biopsy was diagnostic in 54 of 65 patients and salivary gland biopsy in 20 of 30. Decreased nerve conduction velocity, increased CSF protein, negative biopsy findings, and false immunolabeling of amyloid deposits were the main causes of diagnostic errors. We conclude that DNA testing, which is the most reliable test for TTR-FAP, should be performed in patients with a progressive length-dependent small fiber polyneuropathy of unknown origin, especially when associated with autonomic dysfunction.
Published: 2007
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4. 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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5. Intracellular σ 1 receptor modulates phospholipase C and protein kinase C activities in the brainstem

Author: E. E. Baulieu, François P. Monnet, Marie-Pierre Morin-Surun, T. Collin, Monique Denavit-Saubié, PERIGNON, Alain, Institut de Neurobiologie Alfred Fessard (INAF), Centre National de la Recherche Scientifique (CNRS), Neurobiologie génétique et intégrative (NGI), Laboratoire de Neurobiologie, Université de Picardie Jules Verne (UPJV), Stéroides et système nerveux : physiopathologie moléculaire et clinique, and Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Cytoplasm, Pentazocine, MESH: Pentazocine, Action Potentials, Ligands, Tropomyosin receptor kinase C, Phenazocine, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Ligands, MESH: Animals, 5-HT5A receptor, Virulence Factors, Bordetella, Protein Kinase C, MESH: Action Potentials, Protease-activated receptor 2, Multidisciplinary, Reverse Transcriptase Polymerase Chain Reaction, Biological Sciences, MESH: Receptors, sigma, Isoenzymes, MESH: Phenazocine, Biochemistry, MESH: Isoenzymes, MESH: Respiratory Mechanics, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Type C Phospholipases, Antipsychotic Agents, MESH: GTP-Binding Proteins, Guinea Pigs, In Vitro Techniques, MESH: Virulence Factors, Bordetella, MESH: Pertussis Toxin, Biology, MESH: Guinea Pigs, GTP-Binding Proteins, Protein Kinase C beta, Enzyme-linked receptor, Animals, Receptors, sigma, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], G protein-coupled receptor, G protein-coupled receptor kinase, MESH: Cytoplasm, Liver receptor homolog-1, Cell Membrane, MESH: Protein Kinase C, MESH: Male, MESH: Haloperidol, Neuron-derived orphan receptor 1, Pertussis Toxin, Type C Phospholipases, MESH: Brain Stem, Respiratory Mechanics, Haloperidol, MESH: Antipsychotic Agents, Brain Stem, MESH: Cell Membrane
Abstract: Most physiological effects of σ 1 receptor ligands are sensitive to pertussis toxin, suggesting a coupling with cell membrane-bound G proteins. However, the cloning of the σ 1 receptor has allowed the identification of an intracellular protein anchored on the endoplasmic reticulum. Here, we show, using the isolated adult guinea pig brainstem preparation, that activation of the σ 1 receptor results in its translocation from the cytosol to the vicinity of the cell membrane and induces a robust and rapid decrease in hypoglossal activity, which is mediated by phospholipase C. The subsequent activation of protein kinase C β 1 and β 2 isoforms and the phosphorylation of a protein of the same molecular weight as the cloned σ 1 receptor lead to a desensitization of the σ 1 motor response. Our results indicate that the intracellular σ 1 receptor regulates several components implicated in plasma membrane-bound signal transduction. This might be an example of a mechanism by which an intracellular receptor modulates metabotropic responses.
Published: 1999
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6. Neuroprotection by the synthetic neurosteroid enantiomers ent-PREGS and ent-DHEAS against Aβ25–35 peptide-induced toxicity in vitro and in vivo in mice

Author: Marion Alméras, Fadia El Bitar, Yvette Akwa, Tangui Maurice, Kathiresan Krishnan, Johann Meunier, Vanessa Villard, Douglas F. Covey, Herrada, Anthony, 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), King Faisal Specialist Hospital and Research Center, Mécanismes moléculaires dans les démences neurodégénératives (MMDN), Université Montpellier 2 - Sciences et Techniques (UM2)-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), Washington University in Saint Louis (WUSTL), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)
Subjects: medicine.medical_specialty, Neuroactive steroid, education, Pharmacology, medicine.disease_cause, Neuroprotection, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dehydroepiandrosterone sulfate, In vivo, Internal medicine, medicine, otorhinolaryngologic diseases, 030304 developmental biology, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 3. Good health, Endocrinology, chemistry, Toxicity, Pregnenolone, Pregnenolone sulfate, 030217 neurology & neurosurgery, Oxidative stress, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; RATIONALE:Pregnenolone sulfate (PREGS) and dehydroepiandrosterone sulphate (DHEAS) are pro-amnesic, anti-amnesic and neuroprotective steroids in rodents. In Alzheimer's disease (AD) patient's brains, their low concentrations are correlated with high levels of Aβ and tau proteins. The unnatural enantiomer ent-PREGS enhanced memory in rodents. We investigated here whether ent-PREGS and ent-DHEAS could be neuroprotective in AD models.OBJECTIVE:The effects of PREGS, ent-PREGS, DHEAS and ent-DHEAS against Aβ25-35 peptide-induced toxicity were examined in vitro on B104 neuroblastoma cells and in vivo in mice.METHODS:B104 cells pretreated with the steroids before Aβ25-35 were analysed by flow cytometry measuring cell viability and death processes. Mice injected intracerebroventricularly with Aβ25-35 and the steroids were analysed for their memory abilities. Additionally, lipid peroxidation levels in the hippocampus were measured.RESULTS:ent-PREGS and PREGS significantly attenuated the Aβ25-35-induced decrease in cell viability. Both steroids prevented the Aβ25-35-induced increase in late apoptotic cells. PREGS further attenuated the ratio of necrotic cells. ent-DHEAS and DHEAS significantly reduced the Aβ25-35-induced toxicity and prevented the cells from entering late apoptosis and necrosis. All steroids stimulated neurite outgrowth per se and prevented the Aβ25-35-induced decrease. In vivo, ent-PREGS and ent-DHEAS significantly attenuated the Aβ25-35-induced decrease in memory (spontaneous alternation and passive avoidance) and an increase in lipid peroxidation levels. In contrast to the natural steroids, both enantiomers prevented amnesia when injected 6 h before Aβ25-35 in contrast to the natural steroids.CONCLUSION:The unnatural steroids ent-PREGS and ent-DHEAS are potent neuroprotective agents and could be effective therapeutical tools in AD.
Published: 2014
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7. Mutation of the palmitoylation site of estrogen receptor α in vivo reveals tissue-specific roles for membrane versus nuclear actions

Author: Andrée Krust, Coralie Fontaine, Romain Solinhac, Aurelie Fabre, Pierre Chambon, Lucile Sautier, Sung Hoon Kim, Françoise Lenfant, Daniel Henrion, Emilie Vessieres, Marine Adlanmerini, Pierre Gourdy, Jean-François Arnal, John A. Katzenellenbogen, Anne-Laure Guihot, Philippe Liere, Frédéric Boudou, Philip W. Shaul, Isabelle Raymond-Letron, Anne Abot, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), ANEXPLO, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Chemistry, University of Illinois at Urbana-Champaign [Urbana], University of Illinois System-University of Illinois System, 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 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), Department of Pediatrics, University of Texas Southwestern Medical Center [Dallas], The work at I2MC-INSERM U1048 is supported by Institut National de la Santé et de la Recherche Médicale, Université et CHU de Toulouse, Faculté de Médecine Toulouse-Rangueil, Fondation pour la Recherche Médicale, Fondation de France, Fondation de l'Avenir, Conseil Régional Midi-Pyrénées, and AVIESAN-Astra-Zeneca. The work at INSERM U1083-Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche 6214 is supported by INSERM, CNRS, Centre Hospitalier Universitaire and Université d'Angers, Fondation de France, Fondation de l'Avenir and Conseil Régional Pays de la Loire, Conseil Régional Midi-Pyrénées, and Fondation pour la Recherche Médicale. M.A. and A.A. were supported by grants from the Ministère de la Recherche and Groupe de Réflexion sur la Recherche Cardiovasculaire, respectively. This work was supported by National Institutes of Health Grants DK015556 and HL087564 (to J.A.K. and P.W.S., respectively)., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de pharmacologie et de biologie structurale (IPBS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Estrogen receptor, Mice, Transactivation, Cell Movement, Image Processing, Computer-Assisted, MESH: Animals, MESH: Endothelial Cells, Receptor, MESH: Cell Movement, MESH: Estrogen Receptor alpha, fertility, Regulation of gene expression, Multidisciplinary, Immunohistochemistry, MESH: Image Processing, Computer-Assisted, Cell biology, PNAS Plus, MESH: Uterus, Female, vascular effects nongenomic effects, MESH: Computational Biology, MESH: Ovary, MESH: Cell Nucleus, medicine.medical_specialty, MESH: Mice, Transgenic, Steroid hormone receptor, Lipoylation, Blotting, Western, MESH: Receptor Cross-Talk, MESH: Lipoylation, Mice, Transgenic, Biology, genomic actions, In vivo, MESH: Analysis of Variance, Internal medicine, medicine, Animals, Point Mutation, MESH: Blotting, Western, MESH: Mice, MESH: Point Mutation, Cell Nucleus, Analysis of Variance, Cell Membrane, Ovary, Uterus, Estrogen Receptor alpha, Wild type, Computational Biology, Endothelial Cells, MESH: Immunohistochemistry, Receptor Cross-Talk, Microarray Analysis, MESH: Microarray Analysis, Endocrinology, MESH: Female, Estrogen receptor alpha, MESH: Cell Membrane
Abstract: International audience; Estrogen receptor alpha (ERα) activation functions AF-1 and AF-2 classically mediate gene transcription in response to estradiol (E2). A fraction of ERα is targeted to plasma membrane and elicits membrane-initiated steroid signaling (MISS), but the physiological roles of MISS in vivo are poorly understood. We therefore generated a mouse with a point mutation of the palmitoylation site of ERα (C451A-ERα) to obtain membrane-specific loss of function of ERα. The abrogation of membrane localization of ERα in vivo was confirmed in primary hepatocytes, and it resulted in female infertility with abnormal ovaries lacking corpora lutea and increase in luteinizing hormone levels. In contrast, E2 action in the uterus was preserved in C451A-ERα mice and endometrial epithelial proliferation was similar to wild type. However, E2 vascular actions such as rapid dilatation, acceleration of endothelial repair, and endothelial NO synthase phosphorylation were abrogated in C451A-ERα mice. A complementary mutant mouse lacking the transactivation function AF-2 of ERα (ERα-AF2(0)) provided selective loss of function of nuclear ERα actions. In ERα-AF2(0), the acceleration of endothelial repair in response to estrogen-dendrimer conjugate, which is a membrane-selective ER ligand, was unaltered, demonstrating integrity of MISS actions. In genome-wide analysis of uterine gene expression, the vast majority of E2-dependent gene regulation was abrogated in ERα-AF2(0), whereas in C451A-ERα it was nearly fully preserved, indicating that membrane-to-nuclear receptor cross-talk in vivo is modest in the uterus. Thus, this work genetically segregated membrane versus nuclear actions of a steroid hormone receptor and demonstrated their in vivo tissue-specific roles.
Published: 2013
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8. Prevention of obesity and insulin resistance by estrogens requires ERα activation function-2 (ERαAF-2), whereas ERαAF-1 is dispensable

Author: Philippe Liere, Pierre Gourdy, S. Handgraaf, Jean-François Arnal, Rémy Burcelin, Pierre Chambon, Elodie Riant, Andrée Krust, Aurelie Fabre, Aurélie Waget, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 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), Service de Diabétologie, Maladies Métaboliques et Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Diabétologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Simon, Marie Francoise
Subjects: Blood Glucose, Male, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Estrogen receptor, MESH: Mice, Knockout, MESH: Hepatocytes, Mice, 0302 clinical medicine, Adipocytes, Insulin, Glucose homeostasis, MESH: Obesity, MESH: Animals, MESH: Estrogen Receptor alpha, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Mice, Knockout, 0303 health sciences, Estradiol, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Insulin Resistance, Female, MESH: Estradiol, medicine.medical_specialty, Normal diet, medicine.drug_class, 030209 endocrinology & metabolism, MESH: Insulin, Biology, 03 medical and health sciences, Insulin resistance, Commentaries, Internal medicine, Glucose Intolerance, Internal Medicine, medicine, Animals, Obesity, MESH: Mice, MESH: Adipocytes, MESH: Glucose Intolerance, 030304 developmental biology, Estrogen Receptor alpha, medicine.disease, MESH: Male, Endocrinology, Nuclear receptor, Estrogen, Hepatocytes, MESH: Blood Glucose, Insulin Resistance, Estrogen receptor alpha, MESH: Female
Abstract: International audience; The beneficial metabolic actions of estrogen-based therapies are mainly mediated by estrogen receptor α (ERα), a nuclear receptor that regulates gene transcription through two activation functions (AFs): AF-1 and AF-2. Using mouse models deleted electively for ERαAF-1 (ERαAF-1°) or ERαAF-2 (ERαAF-2°), we determined their respective roles in the actions of estrogens on body composition and glucose homeostasis in response to either a normal diet or a high-fat diet (HFD). ERαAF-2° males and females developed accelerated weight gain, massive adiposity, severe insulin resistance, and glucose intolerance--quite reminiscent of the phenotype observed in mice deleted for the entire ERα protein (ERα(-/-)). In striking contrast, ERαAF-1° and wild-type (wt) mice shared a similar metabolic phenotype. Accordingly, 17β-estradiol administration regulated key metabolic genes in insulin-sensitive tissues and conferred a strong protection against HFD-induced metabolic disturbances in wt and ERαAF-1° ovariectomized mice, whereas these actions were totally abrogated in ERαAF-2° and ERα(-/-) mice. Thus, whereas both AFs have been previously shown to contribute to endometrial and breast cancer cell proliferation, the protective effect of estrogens against obesity and insulin resistance depends on ERαAF-2 but not ERαAF-1, thereby delineating new options for selective modulation of ERα.
Published: 2013
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9. The neuronal endopeptidase ECEL1 is associated with a distinct form of recessive distal arthrogryposis

Author: André Mégarbané, Cécile Laroche, Isabelle Marty, Klaus Dieterich, Nicole Monnier, Damien Sternberg, Pierre-Simon Jouk, Jie Zhou, Susana Quijano-Roy, Daniela Avila Smirnow, Pascale Marcorelles, Robert Carlier, Sylvie Odent, Brigitte Estournet, Julien Fauré, Norma B. Romero, Sandra Mercier, Judith Melki, Joël Lunardi, INSERM U836, équipe 4, Muscles et pathologies, 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)-Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM)-Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Génétique et Procréation, CHU Grenoble-CHU Grenoble-Centre de Référence des Anomalies et du Développement, CHU Grenoble-Hôpital Couple Enfant-Hôpital Couple Enfant, Service de Pédiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP]-Centre de Référence Maladies Neuromusculaires (GNMH), Centre d’Investigation Clinique 1429 [Garches] (CIC 1429), Hôpital Raymond Poincaré [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire de Biochimie Génétique et Moléculaire, CHU Grenoble-Institut de Biologie et de Pathologie (IBP)-CHU Grenoble-Institut de Biologie et de Pathologie (IBP), Centre de Référence des Anomalies et du Développement, CHU Grenoble-Hôpital Couple Enfant, Service d'Imagerie Médicale [Raymond-Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Service de Pédiatrie médicale [CHU Limoges], CHU Limoges, CHRU Brest - Laboratoire d'Anatomo-Pathologie (CHU - AnaPath), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Unité de génétique médicale, Université Saint-Joseph de Beyrouth (USJ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'Anatomopathologie, Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-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), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Génétique et Procréation, CHU Grenoble, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Association Française contre les Pyopathies, PHRC (AOM 10181), Inserm, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Roux-Buisson, Nathalie
Subjects: Central Nervous System, Pathology, Genetic Linkage, [SDV.GEN] Life Sciences [q-bio]/Genetics, medicine.disease_cause, Compound heterozygosity, Endothelins, Consanguinity, Mice, 0302 clinical medicine, MESH: Embryonic Development, MESH: Animals, 10. No inequality, Genetics (clinical), Arthrogryposis, Motor Neurons, 0303 health sciences, Mutation, Homozygote, Chromosome Mapping, Metalloendopeptidases, General Medicine, Anatomy, Muscle atrophy, 3. Good health, Pedigree, Phenotype, medicine.symptom, MESH: Motor Neurons, MESH: Homozygote, medicine.hormone, medicine.medical_specialty, MESH: Mutation, MESH: Pedigree, MESH: Arthrogryposis, MESH: Genetic Linkage, MESH: Metalloendopeptidases, Embryonic Development, Genes, Recessive, Biology, MESH: Phenotype, 03 medical and health sciences, Genetics, medicine, MESH: Central Nervous System, Animals, Humans, Molecular Biology, MESH: Mice, MESH: Genes, Recessive, 030304 developmental biology, Muscle contracture, MESH: Consanguinity, [SDV.GEN]Life Sciences [q-bio]/Genetics, Arthrogryposis multiplex congenita, MESH: Humans, Heterozygote advantage, MESH: Chromosome Mapping, 030217 neurology & neurosurgery
Abstract: International audience; Distal arthrogryposis (DA) is a heterogeneous subgroup of arthrogryposis multiplex congenita (AMC), a large family of disorders characterized by multiple congenital joint limitations due to reduced fetal movements. DA is mainly characterized by contractures afflicting especially the distal extremities without overt muscular or neurological signs. Although a limited number of genes mostly implicated in the contractile apparatus have been identified in DA, most patients failed to show mutations in currently known genes. Using a pangenomic approach, we demonstrated linkage of DA to chromosome 2q37 in two consanguineous families and the endothelin-converting enzyme like 1 (ECEL1) gene present in this region was associated with DA. Screening of a panel of 20 families with non-specific DA identified seven homozygous or compound heterozygous mutations of ECEL1 in a total of six families. Mutations resulted mostly in the absence of protein. ECEL1 is a neuronal endopeptidase predominantly expressed in the central nervous system and brain structures during fetal life in mice and human. ECEL1 plays a major role in intramuscular axonal branching of motor neurons in skeletal muscle during embryogenesis. A detailed review of clinical findings of DA patients with ECEL1 mutations revealed a homogeneous and recognizable phenotype characterized by limited knee flexion, flexed third to fifth fingers and severe muscle atrophy predominant on lower limbs and tongue that suggested a common pathogenic mechanism. We described a new and homogenous phenotype of DA associated with ECEL1 that resulted in symptoms involving rather the peripheral than the central nervous system and suggesting a developmental dysfunction.
Published: 2012
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10. Quantitative Fiber Tracking Findings in Cingulum Fibers of Patients with Temporal Lobe Epilepsy

Author: Despina Liacu, Ilana Idy-Peretti, Denis Ducreux, Viviane Bouilleret, Giovanni de Marco, 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), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), 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), Centre de Recherche sur le Sport et le Mouvement (CeRSM), Université Paris Nanterre (UPN), Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), 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 ), Centre de Recherche sur le Sport et le Mouvement ( CeRSM ), and Université Paris Nanterre ( UPN )
Subjects: [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], Analyse du Mouvement en Biomécanique Physiologie et Imagerie, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, [ PHYS.MECA.BIOM ] Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph]
Abstract: International audience; forthcoming
Published: 2012

11. Diffusion Tensor Imaging Tractography Parameters of Limbic System Bundles in Temporal Lobe Epilepsy Patients

Author: Giovanni de Marco, Viviane Bouilleret, Despina Liacu, I. Idy-Peretti, Denis Ducreux, 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), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), 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), Centre de Recherche sur le Sport et le Mouvement (CeRSM), Université Paris Nanterre (UPN), Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), 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 ), Centre de Recherche sur le Sport et le Mouvement ( CeRSM ), and Université Paris Nanterre ( UPN )
Subjects: Pathology, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, tractography, fornix, diffusion tensor imaging (DTI), Nerve Fibers, Myelinated, 030218 nuclear medicine & medical imaging, hippo campal sclerosis (HS), 0302 clinical medicine, Computer-Assisted, Neural Pathways, Limbic System, Cingulum (brain), cingulum, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, [ PHYS.MECA.BIOM ] Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Fornix, Nerve Fibers Myelinated, temporal lobe epilepsy (TLE), Temporal Lobe, medicine.anatomical_structure, Diffusion Tensor Imaging, Female, psychological phenomena and processes, Tractography, Adult, medicine.medical_specialty, Analyse du Mouvement en Biomécanique Physiologie et Imagerie, Sensitivity and Specificity, behavioral disciplines and activities, Temporal lobe, White matter, 03 medical and health sciences, Young Adult, Fractional anisotropy, Image Interpretation, Computer-Assisted, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Radiology, Nuclear Medicine and imaging, [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], Image Interpretation, Hippocampal sclerosis, Epilepsy, business.industry, Reproducibility of Results, medicine.disease, nervous system, Nuclear medicine, business, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: Purpose: To investigate changes in diffusion tensor imaging (DTI) measures in limbic system white matter of patients with temporal lobe epilepsy (TLE) using diffusion tensor tractography. Materials and Methods: DTI metrics including fractional anisotropy (FA), λ1, λ2, λ3, and trace (Tr) coefficients were obtained from tractography for bilateral fornix, superior and inferior cingulum fibers in 18 patients and 10 healthy controls. Hippocampal signal-to-noise ratio (SNR) quantitative analysis was performed in order to confirm the magnetic resonance imaging (MRI) hippocampal lesion presence or absence in TLE patients. Results: Nine patients presented unilateral hippocampal sclerosis (TLE+HS) and nine patients had no signal abnormalities on conventional MRI (TLE−HS). On the ipsilateral seizure side, all three investigated tracts showed significant DTI indices abnormalities in both patient groups when compared with controls, most marked on the inferior cingulum. Contralateral to the seizure side, the three tracts presented significant DTI parameters in only the TLE+HS group when compared with controls. Conclusion: The DTI abnormalities found in the TLE−HS group may suggest that in the inferior cingulum the structural integrity is more affected than in the fornix or superior cingulum white matter bundles. The eigenvalues taken separately add complementary information to the FA and Tr metrics and may be useful indices in better understanding the architectural reorganization of limbic system tracts in TLE patients without HS. J. Magn. Reson. Imaging 2012;36:561–568. © 2012 Wiley Periodicals, Inc.
Published: 2012
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12. Cerebral Peritumoral Oedema Study: Does a Single Dynamic MR Sequence Assessing Perfusion and Permeability Can Help to Differentiate Glioblastoma from Metastasis?

Author: Stoquart-Elsankari Souraya, Giovanni de Marco, Alexis Bruniau, Denis Ducreux, Pierre Lehmann, J.N. Vallée, Guillaume Saliou, Pauline Monet, Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche sur le Sport et le Mouvement (CeRSM), Université Paris Nanterre (UPN), Service de radiologie, CHU Amiens-Picardie, Stéroides et système nerveux : physiopathologie moléculaire et clinique, and Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Pathology, medicine.medical_specialty, Contrast enhancement, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Biopsy, Dynamic mr, Contrast Media, Brain Edema, Permeability, 030218 nuclear medicine & medical imaging, Metastasis, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Image Interpretation, Computer-Assisted, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Functional mr, Radiology, Nuclear Medicine and imaging, Prospective Studies, [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], Aged, Aged, 80 and over, Brain Neoplasms, business.industry, General Medicine, Middle Aged, MR, medicine.disease, Magnetic Resonance Imaging, Perfusion, Cerebral blood volume, Permeability (electromagnetism), Cerebrovascular Circulation, Female, business, Glioblastoma, 030217 neurology & neurosurgery
Abstract: International audience; Our purpose was to differentiate glioblastoma from metastasis using a single dynamic MR sequence to assess perfusion and permeability parameters. 24 patients with glioblastoma or cerebral metastasis with peritumoral oedema were recruited and explored with a 3T MR unit. Post processing used DPTools software. Regions of interest were drawn around contrast enhancement to assess relative cerebral blood volume and permeability parameters. Around the contrast enhancement Glioblastoma present high rCBV with modification of the permeability, metastasis present slight modified rCBV without modification of permeability. In conclusion, peritumoral T2 hypersignal exploration associating morphological MR and functional MR parameters can help to differentiate cerebral metastasis from glioblastoma.
Published: 2012
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13. SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas

Author: Idbaih , Ahmed, Ducray , François, Dehais , Caroline, Courdy , Célia, Carpentier , Catherine, De Bernard , Simon, Uro-Coste , Emmanuelle, Mokhtari , Karima, Jouvet , Anne, Honnorat , Jérôme, Chinot , Olivier, Ramirez , Carole, Beauchesne , Patrick, Benouaich-Amiel , Alexandra, Godard , Joël, Eimer , Sandrine, PARKER , Fabrice, Lechapt-Zalcman , Emmanuelle, Colin , Philippe, Loussouarn , Delphine, Faillot , Thierry, Dam-Hieu , Phong, Elouadhani-Hamdi , Selma, Bauchet , Luc, Langlois , Olivier, Le Guerinel , Caroline, Fontaine , Denys, Vauleon , Elodie, Menei , Philippe, Fotso , Marie Janette Motsuo, Desenclos , Christine, Verrelle , Pierre, Verelle , Pierre, Ghiringhelli , François, Noel , Georges, Labrousse , François, Carpentier , Antoine, Dhermain , Frédéric, Delattre , Jean-Yves, Figarella-Branger , Dominique, Renseigné , Non, 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 ), Département de neurologie 2 - Mazarin, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de Référence Maladie Rare 'Syndromes neurologiques Paranéoplasiques', Hospices Civils de Lyon ( HCL ) -Hopital Neurologique, Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital de Rangueil, Service de Neuropathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de Recherches en Oncologie biologique et Oncopharmacologie ( CRO2 ), Aix Marseille Université ( AMU ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de recherche en neurosciences de Lyon ( CRNL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de Neuro-Oncologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Laboratoire d'Histologie et de Pathologie moléculaire des tumeurs, Université Bordeaux Segalen - Bordeaux 2-EA 2406, Service de neurochirurgie [Bicêtre], Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Université Paris Diderot - Paris 7 ( UPD7 ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service de neurochirurgie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest ( CHU - BREST ), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre d'Études Préhistoire, Antiquité, Moyen-Age ( CEPAM ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service de Neurochirurgie, CHU Nice, CRLCC Eugène Marquis ( CRLCC ), CHU Angers, Micro et nanomédecines biomimétiques ( MINT ), Université d'Angers ( UA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Bretagne Loire ( UBL ), Centre Jean Perrin, CRLCC Jean Perrin, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Centre Paul Strauss, CRLCC Paul Strauss, Homéostasie Cellulaire et Pathologies ( HCP ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -CHU Limoges, Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Université de Limoges ( UNILIM ), Fédération Mazarin, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy ( IGR ), Stéroides et système nerveux : physiopathologie moléculaire et clinique, and Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: MESH : Oligodendroglioma, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH : Male, MESH : Polymorphism, Single Nucleotide, MESH : Humans, MESH : Aged, MESH : Gene Deletion, MESH : Adult, MESH : Genes, p16, MESH : Female, MESH : Middle Aged, MESH : Mutation, MESH : Brain Neoplasms, MESH : Loss of Heterozygosity
Abstract: International audience; Anaplastic oligodendrogliomas (AOD) are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19)(q10;p10), IDH1, IDH2, CIC and FUBP1 mutations).To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA)," has been supported by the Institut National du Cancer (InCA). Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples) were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH) inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD.
Published: 2012
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14. SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas

Author: Emmanuelle Uro-Coste, Luc Bauchet, Jean-Yves Delattre, Caroline Le Guerinel, Phong Dam-Hieu, Christine Desenclos, Alexandra Benouaich-Amiel, Thierry Faillot, Catherine Carpentier, Delphine Loussouarn, Antoine F. Carpentier, Karima Mokhtari, François Labrousse, Georges Noël, Olivier Chinot, Jérôme Honnorat, Simon de Bernard, François Ghiringhelli, Ahmed Idbaih, Pierre Verelle, Selma Elouadhani-Hamdi, Sandrine Eimer, Emmanuelle Lechapt-Zalcman, Dominique Figarella-Branger, Marie Janette Motsuo Fotso, Patrick Beauchesne, Frédéric Dhermain, Joel Godard, Anne Jouvet, Caroline Dehais, Carole Ramirez, Philippe Menei, Célia Courdy, Philippe Colin, Elodie Vauleon, Olivier Langlois, François Ducray, Denys Fontaine, Fabrice Parker, 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), UPMC - Département de neurologie 2 - Mazarin, 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), Centre de Référence Maladie Rare 'Syndromes neurologiques Paranéoplasiques', Hospices Civils de Lyon (HCL)-Hopital Neurologique, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), AltraBio [Lyon], Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Clinique de Neurochirurgie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neuro-Oncologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Services de Neurologie [CHU Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Service de Neurochirurgie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire d'Histologie et de Pathologie moléculaire des tumeurs, Université Bordeaux Segalen - Bordeaux 2-EA 2406, Service de neurochirurgie [Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratoire d'Anatomie Pathologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de neurochirurgie, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de neurochirurgie [AP-HP Hôpital Lariboisière], AP-HP Groupe Hospitalier Lariboisière, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Études Préhistoire, Antiquité, Moyen-Age (CEPAM), Université Nice Sophia Antipolis (... - 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), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Neurochirurgie, Centre Hospitalier Universitaire de Nice (CHU Nice), CRLCC Eugène Marquis (CRLCC), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Service de Neurochirurgie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Hôpital Nord (Saint Etienne), Service de Neurochirurgie [CHU Amiens], CHU Amiens-Picardie, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Paul Strauss, CRLCC Paul Strauss, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-CHU Limoges, Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Université de Limoges (UNILIM), Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), 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), This work is funded by the French Institut National du Cancer (INCa) and part of the national program Cartes d’Identite´ des Tumeurs H (CIT) (http://cit.liguecancer.net/) funded and developed by the Ligue nationale contre le cancer., Sindou, Philippe, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département Neurologie [CHU Toulouse], Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut des Neurosciences de Montpellier (INM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Neurochirurgie [CHRU Besançon], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de neurochirurgie [CHU Angers], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]
Subjects: Male, MESH: Genes, p16, Pathology, Tumor Physiology, Loss of Heterozygosity, Loss of heterozygosity, 0302 clinical medicine, CDKN2A, Gene duplication, Molecular Cell Biology, Basic Cancer Research, MESH: Aged, Multidisciplinary, MESH: Middle Aged, Brain Neoplasms, MESH: Polymorphism, Single Nucleotide, Genomics, Middle Aged, 3. Good health, Neurology, Oncology, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, Medicine, Female, Research Article, Adult, medicine.medical_specialty, IDH1, Histology, MESH: Mutation, Science, Oligodendroglioma, Locus (genetics), [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, IDH2, Polymorphism, Single Nucleotide, 03 medical and health sciences, medicine, Genetics, Cancer Genetics, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Oligodendroglioma, Aged, MESH: Loss of Heterozygosity, MESH: Humans, Genes, p16, Chromosome, MESH: Adult, medicine.disease, MESH: Male, MESH: Gene Deletion, Mutation, MESH: Female, 030217 neurology & neurosurgery, Gene Deletion, Neuroscience
Abstract: International audience; Anaplastic oligodendrogliomas (AOD) are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19)(q10;p10), IDH1, IDH2, CIC and FUBP1 mutations).To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA)," has been supported by the Institut National du Cancer (InCA). Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples) were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH) inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD.
Published: 2012
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15. Diffusion Tensor Changes in Epileptogenic Hippocampus of TLE Patients

Author: G. De Marco, Denis Ducreux, Viviane Bouilleret, I. Idy-Peretti, D. Liacu, P. Masnou, Centre de Recherche sur le Sport et le Mouvement (CeRSM), Université Paris Nanterre (UPN), 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), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), 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), Centre de Recherche sur le Sport et le Mouvement ( CeRSM ), Université Paris Nanterre ( UPN ), Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), and 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 )
Subjects: Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Hippocampal formation, Hippocampus, 030218 nuclear medicine & medical imaging, Epilepsy, 0302 clinical medicine, Computer-Assisted, Hippocampus (mythology), Age of Onset, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, [ PHYS.MECA.BIOM ] Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], medicine.diagnostic_test, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], General Medicine, Middle Aged, Magnetic Resonance Imaging, Temporal Lobe, Neurology, Female, Psychology, psychological phenomena and processes, Adult, Analyse du Mouvement en Biomécanique Physiologie et Imagerie, behavioral disciplines and activities, Temporal lobe, 03 medical and health sciences, Young Adult, Physiology (medical), Image Interpretation, Computer-Assisted, Fractional anisotropy, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], Image Interpretation, Hippocampal sclerosis, Analysis of Variance, Sclerosis, business.industry, Magnetic resonance imaging, medicine.disease, nervous system diseases, EpilepsyTemporal Lobe, Diffusion Magnetic Resonance Imaging, Epilepsy, Temporal Lobe, nervous system, Anisotropy, Neurology (clinical), Nuclear medicine, business, Neuroscience, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: International audience; PURPOSE: Diffusion tensor imaging (DTI) can provide quantitative information of brain abnormalities in patients with temporal lobe epilepsy (TLE) that are not detectable with conventional magnetic resonance imaging (MRI).METHODS: Seventeen patients with medically TLE were selected for the study. The patients and ten healthy subjects underwent 25 directions DTI acquisition. The patients were separated into two groups based on the MRI findings: eight TLE MRI-negative patients with no signal abnormalities on conventional MRI and nine TLE patients with hippocampal sclerosis (HS). Fractional anisotropy (FA), mean diffusivity (MD), and the three diffusivities (lambda(1), lambda(2) and lambda(3)) were measured in bilateral hippocampi of controls, MRI-negative, and HS patients. Comparisons between the three groups were performed for hippocampi ipsi- and contralateral to epileptogenic zone.RESULTS: The ipsilateral hippocampus of MRI-negative patients presented statistical increased anisotropy and no significant difference in diffusivities versus controls. Significant differences in anisotropy and diffusivities were detected between the ipsilateral hippocampus of HS when compared with controls.CONCLUSION: DTI depicted hippocampal abnormalities in TLE patients with a normal conventional MRI different from those found in patients with HS. Diffusivity and anisotropy indices provide significant differences inside hippocampus and should be jointly considered to improve the DTI measurements specificity in TLE patients.
Published: 2010
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16. The immunophilin FKBP52 specifically binds to tubulin and prevents microtubule formation

Author: Chambraud, Béatrice, Belabes, Hamida, Fontaine-Lenoir, Virginie, Fellous, Arlette, Baulieu, Etienne Emile, 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), MAPREG, Hôpital Bicêtre-MAPREG, and ARC (contrat N°3232), FNG
Subjects: neurite differentiation, FK506-Binding Protein, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, macromolecular substances, microtubule dynamics, Cytoskeleton
Abstract: The FK506 binding protein FKBP52 belongs to the large family of immunophilins and is known as a steroid receptor-associated protein. Previous data suggest that FKBP52 is associated with the motor protein dynein and with the cytoskeleton during mitosis. Here we demonstrate a specific and direct interaction between FKBP52 and tubulin. The region of FKBP52 located between aa 267 and 400, which includes the tetratricopeptide repeat domain, is required for tubulin binding. We provide evidence that FKBP52 prevents tubulin polymerization and that an 84 residue sequence located in the C-terminal part of the molecule (aa 375-458) is necessary and sufficient for its microtubule depolymerization activity. In colocalization experiments in PC12 cells, FKBP52 is associated with tubulin in motile cellular compartments. Furthermore, we suggest that, by using siRNA, a decrease of FKBP52 expression in PC12 cells may lead to differentiated cell phenotype characterized by neurite extensions. Collectively, our data define an unexpected property of FKBP52 as a novel regulator of microtubule dynamics. The possible role of microtubule formation and tubulin binding of other immunophilins such as FKBP12 and FKBP51 is discussed.
Published: 2007
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17. The immunophilin FKBP52 specifically binds to tubulin and prevents microtubule formation.: FKBP52 and Tubulin Functional interaction

Author: Chambraud, Béatrice, Belabes, Hamida, Fontaine-Lenoir, Virginie, Fellous, Arlette, Baulieu, Etienne Emile, Chambraud, Béatrice, 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), MAPREG, Hôpital Bicêtre-MAPREG, and ARC (contrat N°3232), FNG
Subjects: neurite differentiation, FK506-Binding Protein, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, macromolecular substances, microtubule dynamics, Cytoskeleton
Abstract: The FK506 binding protein FKBP52 belongs to the large family of immunophilins and is known as a steroid receptor-associated protein. Previous data suggest that FKBP52 is associated with the motor protein dynein and with the cytoskeleton during mitosis. Here we demonstrate a specific and direct interaction between FKBP52 and tubulin. The region of FKBP52 located between aa 267 and 400, which includes the tetratricopeptide repeat domain, is required for tubulin binding. We provide evidence that FKBP52 prevents tubulin polymerization and that an 84 residue sequence located in the C-terminal part of the molecule (aa 375-458) is necessary and sufficient for its microtubule depolymerization activity. In colocalization experiments in PC12 cells, FKBP52 is associated with tubulin in motile cellular compartments. Furthermore, we suggest that, by using siRNA, a decrease of FKBP52 expression in PC12 cells may lead to differentiated cell phenotype characterized by neurite extensions. Collectively, our data define an unexpected property of FKBP52 as a novel regulator of microtubule dynamics. The possible role of microtubule formation and tubulin binding of other immunophilins such as FKBP12 and FKBP51 is discussed.
Published: 2007
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18. Concentrations of estradiol in ewe cerebrospinal fluid are modulated by photoperiod through pineal-dependent mechanisms

Author: Jean-Claude Thiéry, Michael Schumacher, Philippe Delagrange, Didier Lomet, Alain Locatelli, Benoît Malpaux, Philippe Liere, Helene Tricoire, 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), Université Paris-Sud - Paris 11 (UP11), SERVIER, 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 Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Stéroïdes et système nerveux : physiopathologie moléculaire et clinique, 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), Département des Sciences Expérimentales, Institut de Recherches Internationales Servier, and Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: endocrine system, medicine.medical_specialty, PHOTOPERIODE, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Ovariectomy, Photoperiod, Pinealectomy, Biology, GLANDE PINEALE, Pineal Gland, Melatonin, 03 medical and health sciences, Pineal gland, [SCCO]Cognitive science, 0302 clinical medicine, Endocrinology, OESTRADIOL, Internal medicine, Blood plasma, medicine, Animals, [INFO]Computer Science [cs], ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Estrous cycle, 0303 health sciences, Sheep, Estradiol, Luteinizing Hormone, medicine.anatomical_structure, Hypothalamus, Ovariectomized rat, Female, Luteinizing hormone, 030217 neurology & neurosurgery, medicine.drug
Abstract: In the ewe, seasonal anestrus results from an increased responsiveness of the hypothalamus to the negative feedback of estradiol (E2) on the gonadotropic axis under long-day conditions. However, this seasonal effect could also depend upon variable uptake of steroids by the brain. The aim of the present experiment was to compare the concentration of E2 in the blood plasma and in the cerebrospinal fluid (CSF) from the third ventricle in groups of ovariectomized, estradiol treated ewes maintained under short day (SD) or long day (LD) conditions and to study the involvement of the pineal gland in this photoperiodic regulation. Pinealectomized and sham-operated ewes were equipped with an intracerebral cannula to sample the CSF. The plasma E2 concentrations showed no difference between LD and SD in sham-operated and pinealectomized animals. In contrast, in the CSF, E2 concentration was higher in the LD than the SD group, and pinealectomy suppressed this effect of photoperiod. Concomitantly, the stimulatory effect of SD on luteinizing hormone levels observed in sham-operated ewes was abolished by pinealectomy. The results demonstrate that LD increases the E2 concentration in the CSF by a mechanism involving the pineal gland.
Published: 2006
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19. Cell death and axon regeneration of Purkinje cells after axotomy: challenges of classical hypotheses of axon regeneration

Author: Rosine Wehrlé, Marie-Pierre Morel, Abdel M. Ghoumari, Emeline Camand, Lamia Bouslama-Oueghlani, Constantino Sotelo, Isabelle Dusart, Neurobiologie des processus adaptatifs (NPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Neuromorphologie: développement, évolution, Institut National de la Santé et de la Recherche Médicale (INSERM), Stéroides et système nerveux : physiopathologie moléculaire et clinique, and Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Programmed cell death, medicine.medical_treatment, Models, Neurological, Biology, Glial scar, Purkinje Cells, 03 medical and health sciences, Myelin, Myelination, 0302 clinical medicine, medicine, Animals, Neutralization of axon growth inhibitors, Axon, Purkinje cell death, 030304 developmental biology, 0303 health sciences, Cell Death, General Neuroscience, Regeneration (biology), [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Axotomy, Axons, Cell grafting, Nerve Regeneration, medicine.anatomical_structure, nervous system, Peripheral nervous system, Protein kinase C inhibition, Axon sprouting, Neurology (clinical), Neuron, Neuroscience, 030217 neurology & neurosurgery
Abstract: Although adult mammalian neurons are able to regenerate their axons in the peripheral nervous system under certain conditions, they are not able to do it in the central nervous system. The environment surrounding the severed axons appears to be a key factor for axon regeneration. Many studies aiming to enhance axon regeneration in the CNS of adult mammals have successfully manipulated this environment by adding growth permissive molecules and/or neutralizing growth inhibitory molecules. In both cases, the number of axons able to regenerate was low and the different neuronal populations were not equal in their regenerative response, suggesting that manipulation of the environment is not always sufficient. This is particularly well illustrated in the cerebellar system, in which axotomized inferior olivary neurons regenerate when confronted with a permissive environment, whereas mature Purkinje cells do not. The intrinsic ability of a neuron to regenerate its axon is generally correlated with the intensity of its reaction to axotomy (expression of molecules, probability to die). Furthermore, molecules such as GAP-43 (growth-associated molecule) and c-Jun are involved in both axon regeneration and cell death suggesting that these two processes are linked. Surprisingly, Purkinje cells lose their capacity to regenerate their axon (even in the absence of myelin) during development before losing their capacity to react to an axotomy by cell death. These results emphasize the different reactions to axotomy between neuron types and underline that in Purkinje cells, the two cell decisions (axon regeneration and cell death) are differently regulated and therefore not part of the same signaling pathway.
Published: 2005
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20. Bcl-2 protection of axotomized Purkinje cells in organotypic culture is age dependent and not associated with an enhancement of axonal regeneration

Author: Ghoumari, A.M., Wehrle, R., Sotelo, C., Dusart, I., 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), Neurobiologie des processus adaptatifs (NPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Neuromorphologie: développement, évolution, Institut National de la Santé et de la Recherche Médicale (INSERM), Grant sponsors: Institut National de la Santé et de la Recherche Médicale (INSERM, grant U106), and European Community (EC), Biotechnology Programme (CT98-0293).
Subjects: axotomy, cerebellum, Purkinje cell, axonal regeneration, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Bcl-2, neuronal death
Published: 2004
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21. A case report of pseudoprogression followed by complete remission after proton-beam irradiation for a low-grade glioma in a teenager: the value of dynamic contrast-enhanced MRI

Author: Jean-Louis Habrand, Christelle Dufour, Christian Sainte-Rose, Pascale Varlet, Denis Ducreux, Frédéric Dhermain, Candice Meyzer, Jacques Grill, Département de Pédiatrie, Institut Gustave Roussy (IGR), Département de radiothérapie [Gustave Roussy], 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), Centre de Protonthérapie, Service de neuropathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Sainte-Anne, Service de neurochirurgie pédiatrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 (UP11) - IFR93 - Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Sainte-Anne, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and BMC, Ed.
Subjects: lcsh:Medical physics. Medical radiology. Nuclear medicine, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, lcsh:R895-920, Anti-Inflammatory Agents, Contrast Media, Case Report, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Lesion, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Glioma, medicine, Enhancing Lesion, Humans, Radiology, Nuclear Medicine and imaging, Child, Radiation Injuries, Pseudoprogression, medicine.diagnostic_test, Radiotherapy, business.industry, Brain Neoplasms, Magnetic resonance imaging, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Image Enhancement, Magnetic Resonance Imaging, 3. Good health, Surgery, Radiation therapy, Oncology, Radiology Nuclear Medicine and imaging, 030220 oncology & carcinogenesis, Dynamic contrast-enhanced MRI, Prednisone, Radiology, Oligodendroglioma, medicine.symptom, Neoplasm Recurrence, Local, Protons, business, 030217 neurology & neurosurgery
Abstract: A fourteen years-old boy was treated post-operatively with proton therapy for a recurrent low-grade oligodendroglioma located in the tectal region. Six months after the end of irradiation (RT), a new enhancing lesion appeared within the radiation fields. To differentiate disease progression from radiation-induced changes, dynamic susceptibility contrast-enhanced (DSCE) MRI was used with a T2* sequence to study perfusion and permeability characteristics simultaneously. Typically, the lesion showed hypoperfusion and hyperpermeability compared to the controlateral normal brain. Without additional treatment but a short course of steroids, the image disappeared over a six months period allowing us to conclude for a pseudo-progression. The patient is alive in complete remission more than 2 years post-RT.
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21 results on '"Stéroides et système nerveux : physiopathologie moléculaire et clinique"'

1. βAPP Processing Drives Gradual Tau Pathology in an Age-Dependent Amyloid Rat Model of Alzheimer’s Disease

2. Loss-of-function mutations in KIF14 cause severe microcephaly and kidney development defects in humans and zebrafish

3. Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP)

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

5. Intracellular σ 1 receptor modulates phospholipase C and protein kinase C activities in the brainstem

6. Neuroprotection by the synthetic neurosteroid enantiomers ent-PREGS and ent-DHEAS against Aβ25–35 peptide-induced toxicity in vitro and in vivo in mice

7. Mutation of the palmitoylation site of estrogen receptor α in vivo reveals tissue-specific roles for membrane versus nuclear actions

8. Prevention of obesity and insulin resistance by estrogens requires ERα activation function-2 (ERαAF-2), whereas ERαAF-1 is dispensable

9. The neuronal endopeptidase ECEL1 is associated with a distinct form of recessive distal arthrogryposis

10. Quantitative Fiber Tracking Findings in Cingulum Fibers of Patients with Temporal Lobe Epilepsy

11. Diffusion Tensor Imaging Tractography Parameters of Limbic System Bundles in Temporal Lobe Epilepsy Patients

12. Cerebral Peritumoral Oedema Study: Does a Single Dynamic MR Sequence Assessing Perfusion and Permeability Can Help to Differentiate Glioblastoma from Metastasis?

13. SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas

14. SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas

15. Diffusion Tensor Changes in Epileptogenic Hippocampus of TLE Patients

16. The immunophilin FKBP52 specifically binds to tubulin and prevents microtubule formation

17. The immunophilin FKBP52 specifically binds to tubulin and prevents microtubule formation.: FKBP52 and Tubulin Functional interaction

18. Concentrations of estradiol in ewe cerebrospinal fluid are modulated by photoperiod through pineal-dependent mechanisms

19. Cell death and axon regeneration of Purkinje cells after axotomy: challenges of classical hypotheses of axon regeneration

20. Bcl-2 protection of axotomized Purkinje cells in organotypic culture is age dependent and not associated with an enhancement of axonal regeneration

21. A case report of pseudoprogression followed by complete remission after proton-beam irradiation for a low-grade glioma in a teenager: the value of dynamic contrast-enhanced MRI

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21 results on '"Stéroides et système nerveux : physiopathologie moléculaire et clinique"'

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