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22 results on '"Grenoble Institut des Neurosciences ( GIN )"'

1. Impact of Anesthetics on Immune Functions in a Rat Model of Vagus Nerve Stimulation

Author

Chloé Picq, Bruno Bonaz, Valérie Sinniger, Didier Clarençon, Jean-François S. Mayol, INSERM U836, équipe 8, Stress et interactions neurodigestives, Centre de Recherches du Service de Santé des Armées (CRSSA), Service de Santé des Armées-Service de Santé des Armées-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), 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)-Clinique Universitaire d'Hépato-Gastroentérologie, CHU Grenoble-CHU Grenoble, Service de Santé des Armées, Clinique Universitaire d'Hépato-Gastroentérologie, CHU Grenoble, DGA France, and Sinniger, Valérie

Subjects
Central Nervous System, Male, medicine.medical_treatment, Neuroimmunology, Immunofluorescence, General Anesthesia, lcsh:Medicine, NK cells, Pharmacology, Rats, Sprague-Dawley, 0302 clinical medicine, Crohn Disease, Anesthesiology, 030202 anesthesiology, Lymphoid Organs, lcsh:Science, Multidisciplinary, Immune cells, Vagus Nerve, 3. Good health, Cytokines, Medicine, Tumor necrosis factor alpha, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Vagus nerve stimulation, Acetylcholine, Research Article, medicine.drug, Pentobarbital, Vagus Nerve Stimulation, Immunology, T cells, Neurophysiology, Inflammation, Gastroenterology and Hepatology, Anesthetic Mechanisms, Immunomodulation, 03 medical and health sciences, Peripheral Nervous System, medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biology, Anesthetics, business.industry, Inflammatory Bowel Disease, lcsh:R, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Immunologic Subspecialties, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Rats, Vagus nerve, Isoflurane, Immune System, Anesthetic, Immunologic Techniques, lcsh:Q, business, 030217 neurology & neurosurgery, Neuroscience
Abstract

International audience; : Vagus nerve stimulation (VNS) has been successfully performed in animals for the treatment of different experimental models of inflammation. The anti-inflammatory effect of VNS involves the release of acetylcholine by vagus nerve efferent fibers inhibiting pro-inflammatory cytokines (e.g. TNF-α) produced by macrophages. Moreover, it has recently been demonstrated that splenic lymphocytic populations may also be involved. As anesthetics can modulate the inflammatory response, the current study evaluated the effect of two different anesthetics, isoflurane and pentobarbital, on splenic cellular and molecular parameters in a VNS rat model. Spleens were collected for the characterization of lymphocytes sub-populations by flow cytometry and quantification of cytokines secretion after in vitro activation. Different results were observed depending on the anesthetic used. The use of isoflurane displayed a non-specific effect of VNS characterized by a decrease of most splenic lymphocytes sub-populations studied, and also led to a significantly lower TNF-α secretion by splenocytes. However, the use of pentobarbital brought to light immune modifications in non-stimulated animals that were not observed with isoflurane, and also revealed a specific effect of VNS, notably at the level of T lymphocytes' activation. These differences between the two anesthetics could be related to the anti-inflammatory properties of isoflurane. In conclusion, pentobarbital is more adapted than isoflurane in the study of the anti-inflammatory effect of VNS on an anesthetized rat model in that it allows more accurate monitoring of subtle immunomodulatory processes.

Published
2013

2. Brief Subthreshold Events Can Act as Hebbian Signals for Long-Term Plasticity

Author

Jean-Michel Deniau, Elodie Fino, Laurent Venance, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Dynamique et physiopathologie des réseaux neuronaux, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Labex MemoLife, Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Dynamics and Pathophysiology of neuronal networks, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre interdisciplinaire de recherche en biologie (CIRB), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Labex MemoLife, Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and venance, laurent

Subjects
Patch-Clamp Techniques, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Action Potentials, lcsh:Medicine, Nonsynaptic plasticity, Biology, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Postsynaptic potential, Neuroplasticity, Neuroscience/Neuronal Signaling Mechanisms, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Science, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Neuroscience/Cognitive Neuroscience, 0303 health sciences, Neuronal Plasticity, Multidisciplinary, Synaptic scaling, Subthreshold conduction, Neuroscience/Neuronal and Glial Cell Biology, lcsh:R, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Long-term potentiation, Synaptic Potentials, Corpus Striatum, Rats, [SDV] Life Sciences [q-bio], Hebbian theory, nervous system, Anesthesia, Synaptic plasticity, lcsh:Q, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, 030217 neurology & neurosurgery, Research Article
Abstract

BACKGROUND:Action potentials are thought to be determinant for the induction of long-term synaptic plasticity, the cellular basis of learning and memory. However, neuronal activity does not lead systematically to an action potential but also, in many cases, to synaptic depolarizing subthreshold events. This is particularly exemplified in corticostriatal information processing. Indeed, the striatum integrates information from the whole cerebral cortex and, due to the membrane properties of striatal medium spiny neurons, cortical inputs do not systematically trigger an action potential but a wide range of subthreshold postsynaptic depolarizations. Accordingly, we have addressed the following question: does a brief subthreshold event act as a Hebbian signal and induce long-term synaptic efficacy changes? METHODOLOGY/PRINCIPAL FINDINGS:Here, using perforated patch-clamp recordings on rat brain corticostriatal slices, we demonstrate, that brief (30 ms) subthreshold depolarizing events in quasi-coincidence with presynaptic activity can act as Hebbian signals and are sufficient to induce long-term synaptic plasticity at corticostriatal synapses. This "subthreshold-depolarization dependent plasticity" (SDDP) induces strong, significant and bidirectional long-term synaptic efficacy changes at a very high occurrence (81%) for time intervals between pre- and postsynaptic stimulations (Deltat) of -110

Published
2009

3. AutoNeuriteJ: An ImageJ plugin for measurement and classification of neuritic extensions

Author

Jacques Brocard, Jean-Christophe Deloulme, Sylvie Gory-Fauré, Anne Beghin, Annie Andrieux, Benoit Boulan, Eric Denarier, Charlotte Ravanello, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), National University of Singapore (NUS), This work was supported by Institut National de la Santé et de la recherche Médicale, Commissariat à l’Energie Atiomique et aux Energies Alternatives, Université Grenoble Alpes and by awards from the French Agence Nationale de la Recherche to A.A. (2017-CE11-0026 MAMAs). https://www.inserm.fr/ http://www.cea.fr/ https://www.univ-grenoble-alpes.fr/ https://anr.fr/., ANR-17-CE11-0026,MAMAs,Coordination des microtubules et de l'actine par les MAPs structurales(2017), Bodescot, Myriam, and Coordination des microtubules et de l'actine par les MAPs structurales - - MAMAs2017 - ANR-17-CE11-0026 - AAPG2017 - VALID

Subjects
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Imagej plugin, Biochemistry, Hippocampus, Mice, 0302 clinical medicine, Nerve Fibers, Animal Cells, Image Processing, Computer-Assisted, MAP6, Cells, Cultured, Neurons, Mice, Knockout, 0303 health sciences, Neuronal Morphology, Cell Differentiation, medicine.anatomical_structure, Medicine, Cellular Types, Microtubule-Associated Proteins, Neuronal Differentiation, Research Article, Neurite, Imaging Techniques, Science, Neurogenesis, [SCCO.COMP]Cognitive science/Computer science, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Research and Analysis Methods, 03 medical and health sciences, [SCCO.COMP] Cognitive science/Computer science, Tubulins, medicine, Neurites, Animals, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Cell Proliferation, Morphometry, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neuronal Growth, Biology and Life Sciences, Proteins, Cell Biology, Neuronal Dendrites, Axons, Cytoskeletal Proteins, nervous system, Cellular Neuroscience, Neuron, Neuroscience, 030217 neurology & neurosurgery, Software, Developmental Biology
Abstract

Morphometry characterization is an important procedure in describing neuronal cultures and identifying phenotypic differences. This task usually requires labor-intensive measurements and the classification of numerous neurites from large numbers of neurons in culture. To automate these measurements, we wrote AutoNeuriteJ, an imageJ/Fiji plugin that measures and classifies neurites from a very large number of neurons. We showed that AutoNeuriteJ is able to detect variations of neuritic growth induced by several compounds known to affect the neuronal growth. In these experiments measurement of more than 5000 mouse neurons per conditions was obtained within a few hours. Moreover, by analyzing mouse neurons deficient for the microtubule associated protein 6 (MAP6) and wild type neurons we illustrate that AutoNeuriteJ is capable to detect subtle phenotypic difference in axonal length. Overall the use of AutoNeuriteJ will provide rapid, unbiased and accurate measurement of neuron morphologies.

Published
2020

4. Magnetic resonance imaging does not reveal structural alterations in the brain of grapheme-color synesthetes

Author

Dojat, Michel, Pizzagalli, Fabrizio, Hupé, Jean-Michel, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Keck School of Medicine [Los Angeles], University of Southern California (USC), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Central Nervous System, Adult, Male, Imaging Techniques, Permutation, Brain Morphometry, lcsh:Medicine, Social Sciences, Datasets as Topic, Neuroimaging, Research and Analysis Methods, Nervous System, Diagnostic Radiology, Perceptual Disorders, Diagnostic Medicine, Medicine and Health Sciences, Psychology, Humans, lcsh:Science, Brain Mapping, Discrete Mathematics, [SCCO.NEUR]Cognitive science/Neuroscience, Radiology and Imaging, Morphometry, lcsh:R, Biology and Life Sciences, Brain, Magnetic Resonance Imaging, Diffusion Tensor Imaging, Pattern Recognition, Visual, Combinatorics, Physical Sciences, lcsh:Q, Sensory Perception, Female, Anatomy, Voxel-Based Morphometry, Synesthesia, Mathematics, Color Perception, Photic Stimulation, Research Article, Neuroscience
Abstract

Several publications have reported structural changes in the brain of synesthetes compared to controls, either local differences or differences in connectivity. In the present study, we pursued this quest for structural brain differences that might support the subjective experience of synesthesia. In particular, for the first time in this field, we investigated brain folding in comparing 45 sulcal shapes in each hemisphere of control and grapheme-color synesthete populations. To overcome flaws relative to data interpretation based only on p-values, common in the synesthesia literature, we report confidence intervals of effect sizes. Moreover, our statistical maps are displayed without introducing the classical, but misleading, p-value level threshold. We adopt such a methodological procedure to facilitate appropriate data interpretation and promote the "New Statistics" approach. Based on structural or diffusion magnetic resonance imaging data, we did not find any strong cerebral anomaly, in sulci, tissue volume, tissue density or fiber organization that could support synesthetic color experience. Finally, by sharing our complete datasets, we strongly support the multi-center construction of a sufficient large dataset repository for detecting, if any, subtle brain differences that may help understanding how a subjective experience, such as synesthesia, is mentally constructed.

Published
2018

5. Nanoscopic X-ray fluorescence imaging and quantification of intracellular key-elements in cryofrozen Friedreich’s ataxia fibroblasts

Author

Rudy Van Coster, Eline Meul, Brecht Laforce, Björn De Samber, Peter Cloetens, Peter Vandenabeele, Michiel De Bruyne, Riet De Rycke, Sylvain Bohic, Joél Smet, Boel De Paepe, Tom Vanden Berghe, Universiteit Gent = Ghent University [Belgium] (UGENT), VIB-UGent Center for Inflammation Research [Gand, Belgique] (IRC), VIB [Belgium], Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Synchrotron Radiation Facility (ESRF), ORANGE, Colette, and Universiteit Gent = Ghent University (UGENT)

Subjects
0301 basic medicine, Cytoplasm, Luminescence, Glaciology, [SDV]Life Sciences [q-bio], Synchrotron radiation, lcsh:Medicine, PROTEIN, COPPER, Negative Staining, YEAST FRATAXIN, ZINC, 0302 clinical medicine, Limit of Detection, Animal Cells, Ice Cores, Medicine and Health Sciences, Group-Specific Staining, Nanotechnology, OXIDATIVE STRESS, lcsh:Science, Chemical composition, Connective Tissue Cells, Staining, Multidisciplinary, Chemistry, IRON, Physics, Electromagnetic Radiation, Reference Standards, Fluorescence, [SDV] Life Sciences [q-bio], DEFICIENCY, Zinc, medicine.anatomical_structure, Connective Tissue, Physical Sciences, LIBRARY, Prussian Blue Staining, Cellular Types, Anatomy, Cellular Structures and Organelles, Elementary Particles, Research Article, Chemical Elements, Iron, chemistry.chemical_element, X-ray fluorescence, Research and Analysis Methods, 03 medical and health sciences, REDISTRIBUTION, medicine, Humans, Fibroblast, Particle Physics, Nanoscopic scale, Cryopreservation, Photons, CARDIOMYOPATHY, lcsh:R, Spectrometry, X-Ray Emission, Correction, Biology and Life Sciences, Cell Biology, Fibroblasts, 030104 developmental biology, Biological Tissue, Friedreich Ataxia, Specimen Preparation and Treatment, Biophysics, Earth Sciences, lcsh:Q, 030217 neurology & neurosurgery
Abstract

International audience; Synchrotron radiation based nanoscopic X-ray fluorescence (SR nano-XRF) analysis can visualize trace level elemental distribution in a fully quantitative manner within single cells. However, in-air XRF analysis requires chemical fixation modifying the cell's chemical composition. Here, we describe first nanoscopic XRF analysis upon cryogenically frozen (-150 degrees C) fibroblasts at the ID16A-NI 'Nano-imaging' end-station located at the European Synchrotron Radiation Facility (ESRF) in Grenoble (France). Fibroblast cells were obtained from skin biopsies from control and Friedreich's ataxia (FRDA) patients. FRDA is an autosomal recessive disorder with dysregulation of iron metabolism as a key feature. By means of the X-ray Fundamental Parameter (FP) method, including absorption correction of the ice layer deposited onto the fibroblasts, background-corrected mass fraction elemental maps of P, S, Cl, K, Ca, Fe and Zn of entire cryofrozen human fibroblasts were obtained. Despite the presence of diffracting microcrystals in the vitreous ice matrix and minor sample radiation damage effects, clusters of iron-rich hot-spots with similar mass fractions were found in the cytoplasm of both control and FRDA fibroblasts. Interestingly, no significant difference in the mean iron concentration was found in the cytoplasm of FRDA fibroblasts, but a significant decrease in zinc concentration. This finding might underscore metal dysregulation, beyond iron, in cells derived from FRDA patients. In conclusion, although currently having slightly increased limits of detection (LODs) compared to non-cryogenic mode, SR based nanoscopic XRF under cryogenic sample conditions largely obliterates the debate on chemical sample preservation and provides a unique tool for trace level elemental imaging in single cells close to their native state with a superior spatial resolution of 20 nm.

Published
2018

6. Magnetic Resonance Imaging of Cerebral Aspergillosis: Imaging and Pathological Correlations

Author

Marzolf, Guillaume, Sabou, Marcela, Lannes, Béatrice, Cotton, François, Meyronet, David, Galanaud, Damien, Cottier, Jean-Philippe, Grand, Sylvie, Desal, Hubert, Kreutz, Julie, Schenck, Maleka, Meyer, Nicolas, Schneider, Francis, Dietemann, Jean-Louis, Koob, Meriam, Herbrecht, Raoul, Kremer, Stéphane, Zhang, Heye, Département de Neuroradiologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire de Parasitologie et de Mycologie Médicale [Strasbourg], Service de pathologie [CHU Strasbourg], CHU Strasbourg, Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Service de neuroradiologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), 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 Neuroradiologie [St Herblain], Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Département de Radiologie [Liège], Centre Hospitalier Universitaire de Liège (CHU-Liège), Service de Réanimation Médicale [Strasbourg], Laboratoire de biostatistique, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département d'Oncologie et Hématologie [Strasbourg], Université Lumière - Lyon 2 (UL2), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-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), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris, Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Inria de Paris, and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)

Subjects
0301 basic medicine, Male, Pathology, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cerebral arteries, lcsh:Medicine, Corpus callosum, Aspergillosis, Pathology and Laboratory Medicine, Vascular Medicine, Diagnostic Radiology, 0302 clinical medicine, Paranasal Sinuses, Medicine and Health Sciences, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Neuroaspergillosis, Fungal Pathogens, Brain Diseases, Brain Mapping, Multidisciplinary, medicine.diagnostic_test, Radiology and Imaging, Fungal Diseases, Arteries, Middle Aged, Prognosis, Magnetic Resonance Imaging, 3. Good health, medicine.anatomical_structure, Infectious Diseases, Aspergillus, Aspergillus Fumigatus, Medical Microbiology, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Radiology, medicine.symptom, Anatomy, Pathogens, Aneurysms, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Research Article, Adult, medicine.medical_specialty, Imaging Techniques, Brain Morphometry, 030106 microbiology, Neuroimaging, Mycology, Research and Analysis Methods, Microbiology, Lesion, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Vascular Diseases, Pathological, Microbial Pathogens, Aged, Retrospective Studies, business.industry, Diffusion Weighted Imaging, lcsh:R, Organisms, Fungi, Biology and Life Sciences, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Magnetic resonance imaging, Cerebral Arteries, medicine.disease, Molds (Fungi), Abscesses, Paranasal sinuses, Lesions, Cardiovascular Anatomy, Blood Vessels, lcsh:Q, business, 030217 neurology & neurosurgery, Diffusion MRI, Neuroscience
Abstract

Cerebral aspergillosis is associated with a significant morbidity and mortality rate. The imaging data present different patterns and no full consensus exists on typical imaging characteristics of the cerebral lesions. We reviewed MRI findings in 21 patients with cerebral aspergillosis and correlated them to the immune status of the patients and to neuropathological findings when tissue was available. The lesions were characterized by their number, topography, and MRI signal. Dissemination to the brain resulted from direct spread from paranasal sinuses in 8 patients, 6 of them being immunocompetent. Hematogenous dissemination was observed in 13 patients, all were immunosuppressed. In this later group we identified a total of 329 parenchymal abscesses involving the whole brain with a predilection for the corticomedullary junction. More than half the patients had a corpus callosum lesion. Hemorrhagic lesions accounted for 13% and contrast enhancement was observed in 61% of the lesions. Patients with hematogenous dissemination were younger (p = 0.003), had more intracranial lesions (p = 0.0004) and had a higher 12-week mortality rate (p = 0.046) than patients with direct spread from paranasal sinuses. Analysis of 12 aneurysms allowed us to highlight two distinct situations. In case of direct spread from the paranasal sinuses, aneurysms are saccular and located on the proximal artery portions, while the hematogenous dissemination in immunocompromised patients is more frequently associated with distal and fusiform aneurysms. MRI is the exam of choice for cerebral aspergillosis. Number and type of lesions are different according to the mode of dissemination of the infection.

Published
2016

7. Algorithmic design of a noise-resistant and efficient closed-loop deep brain stimulation system: A computational approach

Author

Georgia E. Polychronaki, Olivier David, Stephan Chabardes, Sofia D Karamintziou, George A. Tagaris, Mircea Polosan, Brigitte Piallat, Damianos E. Sakas, George L. Tsirogiannis, Pantelis Stathis, Konstantina S. Nikita, A. L. Custódio, School of Electrical and Computer Engineering, National Technical University of Athens, University of California [Riverside] (UCR), University of California, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm, U1216, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Laboratoire de Psychologie et NeuroCognition (LPNC ), and Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
0301 basic medicine, Obsessive-Compulsive Disorder, Computer science, Deep Brain Stimulation, medicine.medical_treatment, lcsh:Medicine, Stimulation, Signal-To-Noise Ratio, Systems Science, Biochemistry, 0302 clinical medicine, Neuromodulation, Basal ganglia, Medicine and Health Sciences, Premovement neuronal activity, Parkinson, Cortical Synchronization, lcsh:Science, Neurons, Movement Disorders, Multidisciplinary, Parkinson Disease, Neurodegenerative Diseases, Neurochemistry, Dynamical Systems, Neuromodulation (medicine), Signal Filtering, Subthalamic nucleus, Treatment Outcome, medicine.anatomical_structure, Globus pallidus, Neurology, Physical Sciences, [SCCO.PSYC]Cognitive science/Psychology, Engineering and Technology, Algorithms, Research Article, Optimization, Computer and Information Sciences, Deep brain stimulation, Dynamical systems theory, Models, Neurological, Surgical and Invasive Medical Procedures, Feedback, 03 medical and health sciences, Subthalamic Nucleus, Control theory, stimulation protocols, medicine, Humans, Functional electrical stimulation, Stochastic Processes, Functional Electrical Stimulation, [SCCO.NEUR]Cognitive science/Neuroscience, lcsh:R, Biology and Life Sciences, Bandpass Filters, Noise, 030104 developmental biology, Nonlinear Dynamics, Signal Processing, lcsh:Q, Algorithm design, Mathematics, Biomarkers, 030217 neurology & neurosurgery, Neuroscience
Abstract

International audience; Advances in the field of closed-loop neuromodulation call for analysis and modeling approaches capable of confronting challenges related to the complex neuronal response to stimulation and the presence of strong internal and measurement noise in neural recordings. Here we elaborate on the algorithmic aspects of a noise-resistant closed-loop subthalamic nucleus deep brain stimulation system for advanced Parkinson’s disease and treatment-refractory obsessive-compulsive disorder, ensuring remarkable performance in terms of both efficiency and selectivity of stimulation, as well as in terms of computational speed. First, we propose an efficient method drawn from dynamical systems theory, for the reliable assessment of significant nonlinear coupling between beta and high-frequency subthalamic neuronal activity, as a biomarker for feedback control. Further, we present a model-based strategy through which optimal parameters of stimulation for minimum energy desynchronizing control of neuronal activity are being identified. The strategy integrates stochastic modeling and derivative-free optimization of neural dynamics based on quadratic modeling. On the basis of numerical simulations, we demonstrate the potential of the presented modeling approach to identify, at a relatively low computational cost, stimulation settings potentially associated with a significantly higher degree of efficiency and selectivity compared with stimulation settings determined post-operatively. Our data reinforce the hypothesis that model-based control strategies are crucial for the design of novel stimulation protocols at the backstage of clinical applications.

Published
2017

8. Persistence of Cortical Sensory Processing during Absence Seizures in Human and an Animal Model: Evidence from EEG and Intracellular Recordings

Author

Séverine Mahon, Anna Kaminska, Mathilde Chipaux, Stéphane Charpier, Laurent Vercueil, HAL UPMC, Gestionnaire, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rotschild, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’explorations fonctionnelles [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), and 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 National de la Recherche Scientifique (CNRS)

Subjects
Anatomy and Physiology, Pyramidal Tracts, lcsh:Medicine, Electroencephalography, Somatosensory system, Epilepsy, 0302 clinical medicine, Neurobiology of Disease and Regeneration, lcsh:Science, Child, Evoked Potentials, Clinical Neurophysiology, 0303 health sciences, Multidisciplinary, medicine.diagnostic_test, Animal Models, Sensory Systems, Electrophysiology, medicine.anatomical_structure, Neurology, Touch Perception, Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Sensory Perception, France, Evoked Potential, Research Article, Neural Networks, Neurophysiology, Sensory system, Biology, Statistics, Nonparametric, 03 medical and health sciences, Model Organisms, Species Specificity, Event-related potential, Diagnostic Medicine, Genetic model, medicine, Animals, Humans, Ictal, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030304 developmental biology, Analysis of Variance, Pyramidal tracts, lcsh:R, Absence Seizures, Somatosensory Cortex, medicine.disease, Rats, Epilepsy, Absence, Rat, lcsh:Q, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; Absence seizures are caused by brief periods of abnormal synchronized oscillations in the thalamocortical loops, resulting in widespread spike-and-wave discharges (SWDs) in the electroencephalogram (EEG). SWDs are concomitant with a complete or partial impairment of consciousness, notably expressed by an interruption of ongoing behaviour together with a lack of conscious perception of external stimuli. It is largely considered that the paroxysmal synchronizations during the epileptic episode transiently render the thalamocortical system incapable of transmitting primary sensory information to the cortex. Here, we examined in young patients and in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well-established genetic model of absence epilepsy, how sensory inputs are processed in the related cortical areas during SWDs. In epileptic patients, visual event-related potentials (ERPs) were still present in the occipital EEG when the stimuli were delivered during seizures, with a significant increase in amplitude compared to interictal periods and a decrease in latency compared to that measured from non-epileptic subjects. Using simultaneous in vivo EEG and intracellular recordings from the primary somatosensory cortex of GAERS and non-epileptic rats, we found that ERPs and firing responses of related pyramidal neurons to whisker deflection were not significantly modified during SWDs. However, the intracellular subthreshold synaptic responses in somatosensory cortical neurons during seizures had larger amplitude compared to quiescent situations. These convergent findings from human patients and a rodent genetic model show the persistence of cortical responses to sensory stimulations during SWDs, indicating that the brain can still process external stimuli during absence seizures. They also demonstrate that the disruption of conscious perception during absences is not due to an obliteration of information transfer in the thalamocortical system. The possible mechanisms rendering the cortical operation ineffective for conscious perception are discussed, but their definite elucidation will require further investigations.

Published
2013

9. An integrated diagnosis strategy for congenital myopathies

Author

Julie Brocard, Isabelle Marty, Nicole Monnier, Marion Gérard, Edoardo Malfatti, Christine Kretz, Maggie C. Walter, Norma B. Romero, Bernard Jost, H. Karasoy, Valérie Biancalana, Nadia Messaddeq, Joël Lunardi, Stéphanie Le Gras, Jocelyn Laporte, Claire Feger, Nasim Vasli, Peter Reilich, Johann Böhm, Ege Üniversitesi, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chaire Génétique Humaine, Collège de France (CdF (institution)), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Neurological, Neurosurgical, and Behavioral Sciences, Thérapie des maladies du muscle strié, 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), DNA Microarrays and Sequencing Platform, ANTE-INSERM U836, équipe 4, Muscles et pathologies, Biochimie Génétique et Moléculaire, CHU Grenoble-CHU Grenoble, INSERM U836, équipe 4, Muscles et pathologies, 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), Department of Neurology, Ege University School of Medicine, Service de Génétique [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), Ludwig-Maximilians-Universität München (LMU)-Friedrich-Baur-Institute, Laboratoire de Diagnostic Génétique [CHU Strasbourg], Université de Strasbourg (UNISTRA)-CHU Strasbourg, Imaging Center, CHU Grenoble, This work was supported by Institut National de la Sante' et de la Recherche Me'dicale (INSERM), Centre national de la recherche scientifique (CNRS), University of Strasbourg, Colle'ge de France and grants from ANR, GIS Institute for rare diseases and IBiSA, Association Francaise contre les myopathies, Muscular Dystrophy Association (United States of America) and the Myotubular Trust. This work was supported by the INSERM, the CNRS, University of Strasbourg, Colle'ge de France and grants from the Agence Nationale de la Recherche (ANR, grant CM-WES), Muscular Dystrophy Association (MDA, grant 2010-52655) and Myotubular Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Collège de France - Chaire Génétique Humaine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Roux-Buisson, Nathalie

Subjects
Male, Pathology, Genetic Screens, Heredity, Biopsy, DNA Mutational Analysis, Gene Identification and Analysis, lcsh:Medicine, [SDV.GEN] Life Sciences [q-bio]/Genetics, Bioinformatics, 0302 clinical medicine, Missense mutation, Exome, lcsh:Science, Exome sequencing, 0303 health sciences, Multidisciplinary, Muscles, Linkage (Genetics), 3. Good health, Pedigree, Phenotype, Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, medicine.symptom, Research Article, Adult, medicine.medical_specialty, Histology, Nonsense mutation, Molecular Sequence Data, Genetic Counseling, Biology, Muscle disorder, Molecular Genetics, 03 medical and health sciences, Nebulin, Muscular Diseases, Genetic Mutation, medicine, Genetics, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Genetic Testing, Myopathy, 030304 developmental biology, Congenital Hereditary Myopathies, RYR1, Clinical Genetics, [SDV.GEN]Life Sciences [q-bio]/Genetics, Base Sequence, Genetic heterogeneity, lcsh:R, Human Genetics, Sequence Analysis, DNA, Mutation, Genetics of Disease, biology.protein, lcsh:Q, 030217 neurology & neurosurgery
Abstract

WOS: 000321738400157, PubMed ID: 23826317, Congenital myopathies are severe muscle disorders affecting adults as well as children in all populations. The diagnosis of congenital myopathies is constrained by strong clinical and genetic heterogeneity. Moreover, the majority of patients present with unspecific histological features, precluding purposive molecular diagnosis and demonstrating the need for an alternative and more efficient diagnostic approach. We used exome sequencing complemented by histological and ultrastructural analysis of muscle biopsies to identify the causative mutations in eight patients with clinically different skeletal muscle pathologies, ranging from a fatal neonatal myopathy to a mild and slowly progressive myopathy with adult onset. We identified RYR1 (ryanodine receptor) mutations in six patients and NEB (nebulin) mutations in two patients. We found novel missense and nonsense mutations, unraveled small insertions/deletions and confirmed their impact on splicing and mRNA/protein stability. Histological and ultrastructural findings of the muscle biopsies of the patients validated the exome sequencing results. We provide the evidence that an integrated strategy combining exome sequencing with clinical and histopathological investigations overcomes the limitations of the individual approaches to allow a fast and efficient diagnosis, accelerating the patient's access to a better healthcare and disease management. This is of particular interest for the diagnosis of congenital myopathies, which involve very large genes like RYR1 and NEB as well as genetic and phenotypic heterogeneity., Institut National de la Sante et de la Recherche Medicale (INSERM)Institut National de la Sante et de la Recherche Medicale (Inserm); Centre national de la recherche scientifique (CNRS)Centre National de la Recherche Scientifique (CNRS); University of Strasbourg; College de France; GIS Institute; Association Francaise contre les myopathiesAssociation Francaise contre les Myopathies; Muscular Dystrophy Association (United States of America)Muscular Dystrophy Association; Myotubular Trust; Agence Nationale de la Recherche (ANR)French National Research Agency (ANR); Muscular Dystrophy Association (MDA)Muscular Dystrophy Association [2010-52655], This work was supported by Institut National de la Sante et de la Recherche Medicale (INSERM), Centre national de la recherche scientifique (CNRS), University of Strasbourg, College de France and grants from ANR, GIS Institute for rare diseases and IBiSA, Association Francaise contre les myopathies, Muscular Dystrophy Association (United States of America) and the Myotubular Trust. This work was supported by the INSERM, the CNRS, University of Strasbourg, College de France and grants from the Agence Nationale de la Recherche (ANR, grant CM-WES), Muscular Dystrophy Association (MDA, grant 2010-52655) and Myotubular Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Published
2012

10. Specific in vivo staining of astrocytes in the whole brain after intravenous injection of sulforhodamine dyes

Author

Boudewijn van der Sanden, Johannes Römer, Mireille Albrieux, Florence Appaix, Antoine Depaulis, Mathieu Maurin, Isabelle Guillemain, Sylvie Boisseau, Sabine Girod, Jean-Claude Vial, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM U836, équipe 9, Dynamique des réseaux synchrones épileptiques, 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), INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement, Laboratoire de Spectrométrie Physique (LSP), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Inserm U836, équipe 7, Nanomédecine et cerveau, FFRE Contrat de projets Etat-région (CPER), and Issartel, Jean-Paul

Subjects
Pathology, Anatomy and Physiology, Mouse, lcsh:Medicine, MESH: Rats, Sprague-Dawley, Biochemistry, Rats, Sprague-Dawley, chemistry.chemical_compound, Mice, 0302 clinical medicine, Molecular Cell Biology, MESH: Animals, Histochemistry, lcsh:Science, Neurons, 0303 health sciences, education.field_of_study, Multidisciplinary, Brain, Electroencephalography, Neurochemistry, Animal Models, MESH: Staining and Labeling, Injections, Intravenous, Cytochemistry, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cellular Types, Intravital microscopy, Research Article, Genetically modified mouse, medicine.medical_specialty, MESH: Rats, Neural Networks, Transgene, Population, Biology, MESH: Rhodamines, MESH: Calcium Signaling, Stain, Neurological System, 03 medical and health sciences, MESH: Brain, Model Organisms, In vivo, MESH: Mice, Inbred C57BL, MESH: Electroencephalography, medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Calcium Signaling, education, MESH: Mice, 030304 developmental biology, Staining and Labeling, Rhodamines, lcsh:R, Sulforhodamine 101, MESH: Injections, Intravenous, Staining, Rats, MESH: Astrocytes, Mice, Inbred C57BL, Neuroanatomy, chemistry, Astrocytes, Cellular Neuroscience, Rat, lcsh:Q, 030217 neurology & neurosurgery, Neuroscience
Abstract

International audience; Fluorescent staining of astrocytes without damaging or interfering with normal brain functions is essential for intravital microscopy studies. Current methods involved either transgenic mice or local intracerebral injection of sulforhodamine 101. Transgenic rat models rarely exist, and in mice, a backcross with GFAP transgenic mice may be difficult. Local injections of fluorescent dyes are invasive. Here, we propose a non-invasive, specific and ubiquitous method to stain astrocytes in vivo. This method is based on iv injection of sulforhodamine dyes and is applicable on rats and mice from postnatal age to adulthood. The astrocytes staining obtained after iv injection was maintained for nearly half a day and showed no adverse reaction on astrocytic calcium signals or electroencephalographic recordings in vivo. The high contrast of the staining facilitates the image processing and allows to quantify 3D morphological parameters of the astrocytes and to characterize their network. Our method may become a reference for in vivo staining of the whole astrocytes population in animal models of neurological disorders.

Published
2011

11. Combining membrane potential imaging with L-glutamate or GABA photorelease

Author

Stephan Gerharz, Jeremy Graham, Kaspar E. Vogt, Marco Canepari, Division of Pharmacology and Neurobiology, Biozentrum [Basel, Suisse], University of Basel (Unibas)-University of Basel (Unibas), Fluorescence Imaging, Electrophysiology and Microscopy, Cairn Research Limited, INSERM U836, équipe 3, Canaux calciques, fonctions et pathologies, 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)-Division of Pharmacology and Neurobiology, University of Basel (Unibas)-University of Basel (Unibas)-Biozentrum [Basel, Suisse], SNSF grant 3100AO_122000, and Canepari, Marco

Subjects
Central Nervous System, Cerebellum, Optical Phenomena, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], hippocampus, Neural Inhibition, neurons, lcsh:Medicine, Ion Channels, Membrane Potentials, chemistry.chemical_compound, Mice, Purkinje Cells, GABA, 0302 clinical medicine, Neurotransmitter, lcsh:Science, gamma-Aminobutyric Acid, Membrane potential, 0303 health sciences, Multidisciplinary, Neuronal Morphology, Chemistry, Voltage imaging, Neurotransmitters, medicine.anatomical_structure, Biochemistry, Calibration, L-glutamate, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Shunting inhibition, Intracellular, medicine.drug, Research Article, cerebellum, Glutamic Acid, Neurophysiology, Neuroimaging, gamma-Aminobutyric acid, Fluorescence, 03 medical and health sciences, Chlorides, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biology, 030304 developmental biology, lcsh:R, Dendrites, Mice, Inbred C57BL, photolysis, Cellular Neuroscience, Synapses, Biophysics, lcsh:Q, Neuron, 030217 neurology & neurosurgery, Neuroscience
Abstract

International audience; Combining membrane potential imaging using voltage sensitive dyes with photolysis of l-glutamate or GABA allows the monitoring of electrical activity elicited by the neurotransmitter at different sub-cellular sites. Here we describe a simple system and some basic experimental protocols to achieve these measurements. We show how to apply the neurotransmitter and how to vary the dimension of the area of photolysis. We assess the localisation of photolysis and of the recorded membrane potential changes by depolarising the dendrites of cerebellar Purkinje neurons with l-glutamate photorelease using different experimental protocols. We further show in the apical dendrites of CA1 hippocampal pyramidal neurons how l-glutamate photorelease can be used to calibrate fluorescence changes from voltage sensitive dyes in terms of membrane potential changes (in mV) and how GABA photorelease can be used to investigate the phenomenon of shunting inhibition. We also show how GABA photorelease can be used to measure chloride-mediated changes of membrane potential under physiological conditions originating from different regions of a neuron, providing important information on the local intracellular chloride concentrations. The method and the proof of principle reported here open the gateway to a variety of important applications where the advantages of this approach are necessary.

Published
2011

12. MicroRNA and target protein patterns reveal physiopathological features of glioma subtypes

Author

Hélène Ipas, Jean-Paul Issartel, Claire Ramus, Laurent Pelletier, Mehdi Dhobb, Didier Wion, Florence deFraipont, François Berger, Isabelle Dupré, Elodie Lages, Catherine Godfraind, Michèle El Atifi, Caroline Salon, Delphine Rolland, Audrey Guttin, Inserm U836, équipe 7, Nanomédecine et cerveau, 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), INSERM U836, équipe 7, Nanomédecine et cerveau, 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)-Clinical Transcriptomics and Proteomics Platform, CHU Grenoble-CHU Grenoble, CHU Grenoble-CHU Grenoble-Laboratoire d'Hématologie Cellulaire et Moléculaire, CHU Grenoble, Service de Pathologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Laboratoire de Neuropathologie, Université Catholique de Louvain = Catholic University of Louvain (UCL)-Clinique Saint-Luc, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-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), Service de Neurochirurgie, CHU Grenoble-Hôpital Michallon, This study was supported by grants from the Ligue contre le Cancer (comité Isère and Ligue Nationale) (http://www.ligue-cancer.net/), the Région Rhône-Alpes(http://www.rhonealpes.fr/), the Lyon, Auvergne, Rhône-Alpes Cancéropole (http://www.canceropole-clara.com/) and the Institut National du Cancer (http://www.e-cancer.fr/)., Issartel, Jean-Paul, and UCL - (SLuc) Service d'anatomie pathologique

Subjects
MESH: Cell Hypoxia, lcsh:Medicine, Bioinformatics, Polymerase Chain Reaction, Heterogeneous-Nuclear Ribonucleoproteins, MESH: Glioma, 0302 clinical medicine, Molecular cell biology, RNA interference, MESH: DNA Methylation, Sirtuin 1, Gene expression, MESH: Sirtuin 1, MESH: CpG Islands, lcsh:Science, Neurological Tumors, Epigenomics, 0303 health sciences, Multidisciplinary, MESH: STAT3 Transcription Factor, PTBP1, Glioma, Cell Hypoxia, CpG site, Oncology, 030220 oncology & carcinogenesis, DNA methylation, Medicine, MESH: Polypyrimidine Tract-Binding Protein, Research Article, Polypyrimidine Tract-Binding Protein, STAT3 Transcription Factor, MESH: Cell Line, Tumor, Oligodendroglioma, Blotting, Western, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, In Vitro Techniques, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, microRNA, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, MESH: Blotting, Western, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, neoplasms, 030304 developmental biology, MESH: Heterogeneous-Nuclear Ribonucleoproteins, MESH: Humans, lcsh:R, Cancers and Neoplasms, MESH: Polymerase Chain Reaction, DNA Methylation, medicine.disease, nervous system diseases, MicroRNAs, Cancer research, CpG Islands, lcsh:Q, MESH: MicroRNAs, Glioblastoma Multiforme
Abstract

International audience; Gliomas such as oligodendrogliomas (ODG) and glioblastomas (GBM) are brain tumours with different clinical outcomes. Histology-based classification of these tumour types is often difficult. Therefore the first aim of this study was to gain microRNA data that can be used as reliable signatures of oligodendrogliomas and glioblastomas. We investigated the levels of 282 microRNAs using membrane-array hybridisation and real-time PCR in ODG, GBM and control brain tissues. In comparison to these control tissues, 26 deregulated microRNAs were identified in tumours and the tissue levels of seven microRNAs (miR-21, miR-128, miR-132, miR-134, miR-155, miR-210 and miR-409-5p) appropriately discriminated oligodendrogliomas from glioblastomas. Genomic, epigenomic and host gene expression studies were conducted to investigate the mechanisms involved in these deregulations. Another aim of this study was to better understand glioma physiopathology looking for targets of deregulated microRNAs. We discovered that some targets of these microRNAs such as STAT3, PTBP1 or SIRT1 are differentially expressed in gliomas consistent with deregulation of microRNA expression. Moreover, MDH1, the target of several deregulated microRNAs, is repressed in glioblastomas, making an intramitochondrial-NAD reduction mediated by the mitochondrial aspartate-malate shuttle unlikely. Understanding the connections between microRNAs and bioenergetic pathways in gliomas may lead to identification of novel therapeutic targets.

Published
2011

13. The spatial organization of proton and lactate transport in a rat brain tumor

Author

Emmanuelle Grillon, Régine Farion, Michel De Waard, Chantal Rémy, Mark Donowitz, Chung Ming Tse, Jonathan A. Coles, Katell Fablet, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Departments of Physiology and Medicine, Gastroenterology Division, Johns Hopkins University School of Medicine, Centre for Biophotonics, University of Strathclyde [Glasgow], and Dojat, Michel

Subjects
Lactate transport, Anatomy and Physiology, Cancer Treatment, lcsh:Medicine, Biochemistry, Energy-Producing Processes, 0302 clinical medicine, Molecular Cell Biology, Neurobiology of Disease and Regeneration, Drug Discovery, Basic Cancer Research, Tumor Cells, Cultured, Pathology, Tissue Distribution, lcsh:Science, Cells, Cultured, 0303 health sciences, Multidisciplinary, biology, Chemistry, Brain Neoplasms, Glioma, Head and Neck Tumors, Extracellular Matrix, Cell Motility, Oncology, 030220 oncology & carcinogenesis, Carbohydrate Metabolism, Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Protons, Intracellular, Cell Division, Research Article, Monocarboxylic Acid Transporters, Cell Physiology, Drugs and Devices, Sodium-Hydrogen Exchangers, Histology, Drug Research and Development, Biophysics, Bioenergetics, Models, Biological, 03 medical and health sciences, Diagnostic Medicine, Carbonic anhydrase, medicine, Extracellular, Cell Adhesion, Cancer Detection and Diagnosis, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Lactic Acid, Biology, Ion transporter, 030304 developmental biology, Ion Transport, lcsh:R, Cancers and Neoplasms, Biological Transport, medicine.disease, Rats, Sodium–hydrogen antiporter, Metabolism, biology.protein, lcsh:Q, Cotransporter, Physiological Processes, Energy Metabolism, Neuroscience
Abstract

Tumors create a heterogeneous acidic microenvironment which assists their growth and which must be taken into account in the design of drugs and their delivery. In addition, the acidic extracellular pH (pHe) is itself exploited in several experimental techniques for drug delivery. The way the acidity is created is not clear. We report here the spatial organization of key proton-handling proteins in C6 gliomas in rat brain. The mean profiles across the tumor rim of the Na+/H+ exchanger NHE1, and the lactate-H+ cotransporter MCT1, both showed peaks. NHE1, which is important for extension and migration of cells in vitro, showed a peak 1.55 times higher than in extratumoural tissue at 0.33 mm from the edge. MCT1 had a broader peak, further into the tumor (maximum 1.76 fold at 1.0 mm from the edge). In contrast, MCT4 and the carbonic anhydrase CAIX, which are associated with hypoxia, were not significantly upregulated in the rim. The spatial distribution of MCT4 was highly correlated with that of CAIX, suggesting that their expression is regulated by the same factors. Since protons extruded by NHE1 diffuse away through extracellular clefts, NHE1 requires a continuous source of intracellular protons. From the stoichiometries of metabolic pathways that produce or consume H+, and the greater availability of glucose compared to oxygen in most parts of a tumor, we support the classic view that most of the net proton efflux from C6 gliomas originates in glycolytic formation of lactate and H+ inside the tumor, but add that some lactate is taken up into cells in the rim on MCT1, and some lactate diffuses away, leaving its associated protons available to re-enter cells for extrusion on NHE1. Therapeutic inhibition of NHE1, MCT1 or CAIX is predicted to affect different parts of a tumor.

Published
2010

14. Mutation of Ser172 in Yeast β Tubulin Induces Defects in Microtubule Dynamics and Cell Division

Author

Annie Andrieux, Anne Fourest-Lieuvin, Eric Denarier, Jacques Brocard, Fabrice Caudron, Jenny-Constanza Thibout-Quintana, Institute of Biochemistry, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe Physiopathologie du Cytosquelette (GPC), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), ANR Tyr-TIPs (Blan07-2_187328) La Ligue contre le cancer (R07Job) ARC(4892 and 7927), ANR-07-BLAN-0045,Tyr-TIPs,Cell regulations at microtubule +ends: shifting from a Darwinist to a deterministic view of microtubule organization and of cell morphogenesis(2007), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Andrieux, Annie, and Blanc - Cell regulations at microtubule +ends: shifting from a Darwinist to a deterministic view of microtubule organization and of cell morphogenesis - - Tyr-TIPs2007 - ANR-07-BLAN-0045 - BLANC - VALID

Subjects
Cell division, MESH: Sequence Homology, Amino Acid, Cell Biology/Cell Growth and Division, lcsh:Medicine, MESH: Cell Cycle, MESH: Amino Acid Sequence, MESH: Tubulin, medicine.disease_cause, Microtubules, 0302 clinical medicine, Tubulin, Serine, Phosphorylation, lcsh:Science, 0303 health sciences, Mutation, Multidisciplinary, MESH: Microtubules, Cell Cycle, MESH: Saccharomyces cerevisiae, Cell biology, Spindle checkpoint, MESH: Cell Division, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cell Division, Research Article, MESH: Mutation, Saccharomyces cerevisiae, Molecular Sequence Data, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 03 medical and health sciences, Microtubule, Cell Biology/Cytoskeleton, medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Serine, Amino Acid Sequence, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Cyclin-dependent kinase 1, MESH: Molecular Sequence Data, MESH: Phosphorylation, Sequence Homology, Amino Acid, Cell growth, lcsh:R, Cell Biology, biology.organism_classification, Molecular biology, biology.protein, lcsh:Q, 030217 neurology & neurosurgery
Abstract

Ser172 of β tubulin is an important residue that is mutated in a human brain disease and phosphorylated by the cyclin-dependent kinase Cdk1 in mammalian cells. To examine the role of this residue, we used the yeast S. cerevisiae as a model and produced two different mutations (S172A and S172E) of the conserved Ser172 in the yeast β tubulin Tub2p. The two mutants showed impaired cell growth on benomyl-containing medium and at cold temperatures, altered microtubule (MT) dynamics, and altered nucleus positioning and segregation. When cytoplasmic MT effectors Dyn1p or Kar9p were deleted in S172A and S172E mutants, cells were viable but presented increased ploidy. Furthermore, the two β tubulin mutations exhibited synthetic lethal interactions with Bik1p, Bim1p or Kar3p, which are effectors of cytoplasmic and spindle MTs. In the absence of Mad2p-dependent spindle checkpoint, both mutations are deleterious. These findings show the importance of Ser172 for the correct function of both cytoplasmic and spindle MTs and for normal cell division., PLoS ONE, 5 (10), ISSN:1932-6203

Published
2010

15. ZAP-70 restoration in mice by in vivo thymic electroporation

Author

Lionel F. Poulin, Magali Irla, Catherine Nguyen, Lee Leserman, Murielle Saade, Adrien Kissenpfennig, Patrice N. Marche, Evelyne Jouvin-Marche, François Berger, Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infection and Immunity, Queen's University [Kingston, Canada], Centre d'Immunologie de Marseille - Luminy (CIML), INSERM U823, équipe 8 (Immunologie Analytique des Pathologies Chroniques), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), and Nguyen, Catherine

Subjects
Time Factors, Genetic enhancement, T-Lymphocytes, ddc:616.07, Mice, 0302 clinical medicine, Spleen/cytology, Thymus Gland/*cytology, Cytotoxic T cell, Anesthesia, 0303 health sciences, Multidisciplinary, ZAP-70 Protein-Tyrosine Kinase, Electroporation, Electroporation/*methods, Receptors, Antigen, T-Cell/metabolism, Cell Differentiation, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Medicine, Research Article, T-Lymphocytes/cytology, Lymphoid Tissue, Science, T cell, Green Fluorescent Proteins, Immunology, Receptors, Antigen, T-Cell, Thymus Gland, Biology, Transfection, Immunophenotyping, 03 medical and health sciences, In vivo, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Animals, 030304 developmental biology, Green Fluorescent Proteins/metabolism, Severe combined immunodeficiency, Lymphoid Tissue/cytology, T-cell receptor, ZAP-70 Protein-Tyrosine Kinase/deficiency/*metabolism, Electric Conductivity, medicine.disease, T cell differentiation, Cancer research, Spleen
Abstract

International audience; Viral and non-viral vectors have been developed for gene therapy, but their use is associated with unresolved problems of efficacy and safety. Efficient and safe methods of DNA delivery need to be found for medical application. Here we report a new monopolar system of non-viral electro-gene transfer into the thymus in vivo that consists of the local application of electrical pulses after the introduction of the DNA. We assessed the proof of concept of this approach by correcting ZAP-70 deficient severe combined immunodeficiency (SCID) in mice. The thymic electro-gene transfer of the pCMV-ZAP-70-IRES-EGFP vector in these mice resulted in rapid T cell differentiation in the thymus with mature lymphocytes detected by three weeks in secondary lymphoid organs. Moreover, this system resulted in the generation of long-term functional T lymphocytes. Peripheral reconstituted T cells displayed a diversified T cell receptor (TCR) repertoire, and were responsive to alloantigens in vivo. This process applied to the thymus could represent a simplified and effective alternative for gene therapy of T cell immunodeficiencies.

Published
2008

16. Synchrotron X ray induced axonal transections in the brain of rats assessed by high-field diffusion tensor imaging tractography

Author

Nicolas Coquery, Audrey Bouchet, Stefan Bartzsch, Benoît Pouyatos, Elke Bräuer-Krisch, Yohan van de Looij, Luc Renaud, Jean A. Laissue, Raphaël Serduc, Géraldine Le Duc, INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, 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), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Synchrotron Radiation Facility (ESRF), Universität Bern [Bern], INSERM U836, équipe 9, Dynamique des réseaux synchrones épileptiques, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), Laboratoire d'imagerie fonctionnelle et métabolique, Ecole Polytechnique Fédérale de Lausanne (EPFL), Service du développement et de la croissance, Hôpitaux Universitaire de Genève, ANR EPIRAD., Universität Bern [Bern] (UNIBE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Serduc, Raphael

Subjects
Anatomy and Physiology, Cancer Treatment, lcsh:Medicine, Nerve Fibers, Myelinated, Diagnostic Radiology, Myelin, lcsh:Science, Myelin Sheath, Multidisciplinary, Chemistry, X-ray, Brain, Animal Models, Microbeam, Magnetic Resonance Imaging, Diffusion Tensor Imaging, medicine.anatomical_structure, Neurology, Oncology, Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Radiology, Research Article, External capsule, Radiation Therapy, 610 Medicine & health, Brain damage, Radiation Dosage, Neurological System, White matter, Model Organisms, medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Irradiation, Biology, Epilepsy, business.industry, X-Rays, lcsh:R, Axons, Rats, Neuroanatomy, nervous system, Rat, 570 Life sciences, biology, lcsh:Q, Nuclear medicine, business, Synchrotrons, Diffusion MRI, Biomedical engineering
Abstract

International audience; Since approximately two thirds of epileptic patients are non-eligible for surgery, local axonal fiber transections might be of particular interest for them. Micrometer to millimeter wide synchrotron-generated X-ray beamlets produced by spatial fractionation of the main beam could generate such fiber disruptions non-invasively. The aim of this work was to optimize irradiation parameters for the induction of fiber transections in the rat brain white matter by exposure to such beamlets. For this purpose, we irradiated cortex and external capsule of normal rats in the antero-posterior direction with a 4 mm×4 mm array of 25 to 1000 µm wide beamlets and entrance doses of 150 Gy to 500 Gy. Axonal fiber responses were assessed with diffusion tensor imaging and fiber tractography; myelin fibers were examined histopathologically. Our study suggests that high radiation doses (500 Gy) are required to interrupt axons and myelin sheaths. However, a radiation dose of 500 Gy delivered by wide minibeams (1000 µm) induced macroscopic brain damage, depicted by a massive loss of matter in fiber tractography maps. With the same radiation dose, the damage induced by thinner microbeams (50 to 100 µm) was limited to their paths. No macroscopic necrosis was observed in the irradiated target while overt transections of myelin were detected histopathologically. Diffusivity values were found to be significantly reduced. A radiation dose ≤ 500 Gy associated with a beamlet size of < 50 µm did not cause visible transections, neither on diffusion maps nor on sections stained for myelin. We conclude that a peak dose of 500 Gy combined with a microbeam width of 100 µm optimally induced axonal transections in the white matter of the brain.

Published
2014

17. Monitoring Monoclonal Antibody Delivery in Oncology: The Example of Bevacizumab

Author

Marie Arlotto, Mireille Mousseau, Guillaume Nugue, Marie Bidart, Laurent Pelletier, François Berger, Inserm U836, équipe 7, Nanomédecine et cerveau, 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), INSERM U836, équipe 7, Nanomédecine et cerveau, 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)-Service d'oncologie médicale, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-CHU Grenoble, Service d'oncologie médicale, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, and Issartel, Jean-Paul

Subjects
Male, Oncology, Epidemiology, medicine.medical_treatment, Cancer Treatment, lcsh:Medicine, Angiogenesis Inhibitors, Targeted therapy, chemistry.chemical_compound, 0302 clinical medicine, Neoplasms, Breast Tumors, lcsh:Science, Neurological Tumors, 0303 health sciences, Multidisciplinary, Brain Neoplasms, Clinical Pharmacology, Antibodies, Monoclonal, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Bevacizumab, Vascular endothelial growth factor, Treatment Outcome, 030220 oncology & carcinogenesis, Monoclonal, Medicine, Biomarker (medicine), Female, Research Article, Test Evaluation, medicine.drug, Adult, Drugs and Devices, medicine.medical_specialty, medicine.drug_class, Antineoplastic Agents, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antibodies, Monoclonal, Humanized, Monoclonal antibody, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antibody Therapy, Diagnostic Medicine, Internal medicine, Glioma, medicine, Humans, Pharmacokinetics, Aged, 030304 developmental biology, Clinical Genetics, business.industry, Pharmacoepidemiology, lcsh:R, Personalized Medicine, Cancers and Neoplasms, medicine.disease, Biomarker Epidemiology, chemistry, Pharmacodynamics, lcsh:Q, business
Abstract

International audience; Developing therapeutic monoclonal antibodies paves the way for new strategies in oncology using targeted therapy which should improve specificity. However, due to a lack of biomarkers, a personalized therapy scheme cannot always be applied with monoclonal antibodies. As a consequence, the efficacy or side effects associated with this type of treatment often appear to be sporadic. Bevacizumab is a therapeutic monoclonal antibody targeting Vascular Endothelial Growth Factor (VEGF). It is used to limit tumor vascularization. No prognosis or response biomarker is associated with this antibody, we therefore assessed whether the administration protocol could be a possible cause of heterogeneous responses (or variable efficacy). To do this, we developed a bevacizumab assay with a broad sensitivity range to measure blood bevacizumab concentrations. We then analyzed bevacizumab concentrations in 17 patients throughout the first quarter of treatment. In line with previously published data, average blood concentrations were 88+/-27 mg/L following the first dose administered, and 213+/-105 mg/L after the last (6(th)) dose administered. However, the individual values were scattered, with a mean 4-fold difference between the lowest and the highest concentration for each dose administered. We demonstrated that the bevacizumab administration schedule results in a high inter-individual variability in terms of blood concentrations. Comparison of assay data with clinical data indicates that blood concentrations above the median are associated with side effects, whereas values below the median favor inefficacy. In conclusion, bevacizumab-based therapy could benefit from a personalized administration schedule including follow-up and adjustment of circulating bevacizumab concentrations.

Published
2013

18. Striatal Molecular Signature of Subchronic Subthalamic Nucleus High Frequency Stimulation in Parkinsonian Rat

Author

Pascal Salin, Nicolas Boulanger, Catherine Nguyen, Pascal Rihet, Sylviane Lortet, Lydia Kerkerian-Le Goff, Emilie Lacombe, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Mécanique et Gravitation, Université de Mons-Hainaut, Transcriptomic Genomic Marseille-Luminy (TGML), Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Microarrays, Deep Brain Stimulation, medicine.medical_treatment, lcsh:Medicine, Striatum, Pharmacology, Levodopa, Molecular cell biology, 0302 clinical medicine, Nucleic Acids, Neurobiology of Disease and Regeneration, Cluster Analysis, lcsh:Science, Neurons, 0303 health sciences, Movement Disorders, Multidisciplinary, Behavior, Animal, Metabotropic glutamate receptor 4, Dopaminergic, Animal Models, Neurotransmitters, Denervation, 3. Good health, Parkinson disease, Subthalamic nucleus, Neurology, Neuronal differentiation, Medicine, Metabolic Networks and Pathways, Research Article, medicine.drug, Deep brain stimulation, DNA transcription, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Neuroprotection, 03 medical and health sciences, Model Organisms, Subthalamic Nucleus, Dopamine, medicine, Animals, 030304 developmental biology, Gene Expression Profiling, lcsh:R, Corpus Striatum, Electric Stimulation, Rats, Gene regulation, nervous system diseases, Neostriatum, Disease Models, Animal, Gene Expression Regulation, nervous system, Rat, RNA, lcsh:Q, Gene expression, Molecular Neuroscience, 030217 neurology & neurosurgery, Neuroscience
Abstract

International audience; This study addresses the molecular mechanisms underlying the action of subthalamic nucleus high frequency stimulation (STN-HFS) in the treatment of Parkinson's disease and its interaction with levodopa (L-DOPA), focusing on the striatum. Striatal gene expression profile was assessed in rats with nigral dopamine neuron lesion, either treated or not, using agilent microarrays and qPCR verification. The treatments consisted in anti-akinetic STN-HFS (5 days), chronic L-DOPA treatment inducing dyskinesia (LIDs) or the combination of the two treatments that exacerbated LIDs. STN-HFS modulated 71 striatal genes. The main biological processes associated with the differentially expressed gene products include regulation of growth, of apoptosis and of synaptic transmission, and extracellular region is a major cellular component implicated. In particular, several of these genes have been shown to support survival or differentiation of striatal or of dopaminergic neurons. These results indicate that STN HFS may induce widespread anatomo-functional rearrangements in the striatum and create a molecular environment favorable for neuroprotection and neuroplasticity. STN-HFS and L-DOPA treatment share very few common gene regulation features indicating that the molecular substrates underlying their striatal action are mostly different; among the common effects is the down-regulation of Adrb1, which encodes the adrenergic beta-1-receptor, supporting a major role of this receptor in Parkinson's disease. In addition to genes already reported to be associated with LIDs (preprodynorphin, thyrotropin-releasing hormone, metabotropic glutamate receptor 4, cannabinoid receptor 1), the comparison between DOPA and DOPA/HFS identifies immunity-related genes as potential players in L-DOPA side effects.

Published
2013

19. Levodopa Effects on Hand and Speech Movements in Patients with Parkinson’s Disease: A fMRI Study

Author

Alexandre Krainik, Audrey Maillet, Stéphane Thobois, Irène Troprès, Christelle Lagrange, Pierre Pollak, Serge Pinto, Bettina Debû, Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), 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), INSERM U836, équipe 5, Neuroimagerie fonctionnelle et perfusion cérébrale, 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)-Neuroradiologie & IRM, CHU Grenoble-CHU Grenoble, INSERM U836, équipe 11, Fonctions cérébrales et neuromodulation, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de neurologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Neurologie C, Hospices Civils de Lyon (HCL)-Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Université de Lyon, Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie des HUG, Hôpitaux Universitaires de Genève (HUG), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), French Health Ministry (PHRC 2005), David, Olivier, and Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ)

Subjects
Male, Speech production, Parkinson's disease, lcsh:Medicine, MESH: Movement, Social and Behavioral Sciences, Magnetic Resonance Imaging/methods, MESH: Magnetic Resonance Imaging, Levodopa, 0302 clinical medicine, Basal ganglia, lcsh:Science, Neurolinguistics, Parkinson Disease/physiopathology, MESH: Aged, MESH: Levodopa, 0303 health sciences, Movement Disorders, MESH: Middle Aged, Multidisciplinary, Supplementary motor area, medicine.diagnostic_test, MESH: Speech, Putamen, fMRI, Speech/drug effects, Parkinson Disease, Middle Aged, Magnetic Resonance Imaging, medicine.anatomical_structure, Neurology, Medicine, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Primary motor cortex, Levodopa/pharmacology, Research Article, Drugs and Devices, Movement, Neuroimaging, Biology, Premotor cortex, 03 medical and health sciences, Movement/drug effects, Neuropharmacology, medicine, Humans, Speech, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, 030304 developmental biology, MESH: Humans, lcsh:R, Linguistics, medicine.disease, MESH: Male, ddc:616.8, lcsh:Q, Functional magnetic resonance imaging, MESH: Female, Neuroscience, MESH: Parkinson Disease, 030217 neurology & neurosurgery
Abstract

International audience; Levodopa (L-dopa) effects on the cardinal and axial symptoms of Parkinson's disease (PD) differ greatly, leading to therapeutic challenges for managing the disabilities in this patient's population. In this context, we studied the cerebral networks associated with the production of a unilateral hand movement, speech production, and a task combining both tasks in 12 individuals with PD, both off and on levodopa (L-dopa). Unilateral hand movements in the off medication state elicited brain activations in motor regions (primary motor cortex, supplementary motor area, premotor cortex, cerebellum), as well as additional areas (anterior cingulate, putamen, associative parietal areas); following L-dopa administration, the brain activation profile was globally reduced, highlighting activations in the parietal and posterior cingulate cortices. For the speech production task, brain activation patterns were similar with and without medication, including the orofacial primary motor cortex (M1), the primary somatosensory cortex and the cerebellar hemispheres bilaterally, as well as the left- premotor, anterior cingulate and supramarginal cortices. For the combined task off L-dopa, the cerebral activation profile was restricted to the right cerebellum (hand movement), reflecting the difficulty in performing two movements simultaneously in PD. Under L-dopa, the brain activation profile of the combined task involved a larger pattern, including additional fronto-parietal activations, without reaching the sum of the areas activated during the simple hand and speech tasks separately. Our results question both the role of the basal ganglia system in speech production and the modulation of task-dependent cerebral networks by dopaminergic treatment.

Published
2012

20. Increased Phosphorylation of Vimentin in Noninfiltrative Meningiomas

Author

Ali Bouamrani, François Berger, Claire Ramus, Myriam Cubizolles, Laurent Pelletier, Didier Wion, Jean-Paul Issartel, Sabine Brugière, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de neurochirurgie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Ciphergen, Ciphergen Biosystems, Laboratoire de chimie des protéines, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Région Rhône-Alpes, Ligue contre le Cancer, Lyon, Auvergne, Rhône-Alpes Cancéropôle, Institut national du Cancer, and Issartel, Jean-Paul

Subjects
Male, Proteomics, Pathology, Vimentin, Tissue infiltration, 0302 clinical medicine, Biochemistry/Protein Chemistry, Meningeal Neoplasms, Cluster Analysis, Phosphorylation, Oncology/Neuro-Oncology, 0303 health sciences, Multidisciplinary, biology, Middle Aged, 030220 oncology & carcinogenesis, Medicine, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Tissue invasion, Female, Meningioma, Research Article, Adult, medicine.medical_specialty, Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sensitivity and Specificity, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Biology/Cytoskeleton, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Biomarkers, Tumor, otorhinolaryngologic diseases, medicine, Humans, Meningeal Neoplasm, neoplasms, Aged, 030304 developmental biology, medicine.disease, nervous system diseases, Molecular Weight, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Molecular Biology/Post-Translational Regulation of Gene Expression, Tissue extracts, biology.protein
Abstract

International audience; BACKGROUND: Tissue invasion or tissue infiltration are clinical behaviors of a poor-prognosis subset of meningiomas. We carried out proteomic analyses of tissue extracts to discover new markers to accurately distinguish between infiltrative and noninfiltrative meningiomas. METHODOLOGY/PRINCIPAL FINDINGS: Protein lysates of 64 different tissue samples (including two brain-invasive and 32 infiltrative tumors) were submitted to SELDI-TOF mass spectrometric analysis. Mass profiles were used to build up both unsupervised and supervised hierarchical clustering. One marker was found at high levels in noninvasive and noninfiltrative tumors and appeared to be a discriminative marker for clustering infiltrative and/or invasive meningiomas versus noninvasive meningiomas in two distinct subsets. Sensitivity and specificity were 86.7% and 100%, respectively. This marker was purified and identified as a multiphosphorylated form of vimentin, a cytoskeletal protein expressed in meningiomas. CONCLUSIONS/SIGNIFICANCE: Specific forms of vimentin can be surrogate molecular indicators of the invasive/infiltrative phenotype in tumors.

Published
2010

21. Algorithmic design of a noise-resistant and efficient closed-loop deep brain stimulation system: A computational approach.

Author

Karamintziou SD, Custódio AL, Piallat B, Polosan M, Chabardès S, Stathis PG, Tagaris GA, Sakas DE, Polychronaki GE, Tsirogiannis GL, David O, and Nikita KS

Subjects
Cortical Synchronization, Feedback, Humans, Neurons physiology, Nonlinear Dynamics, Obsessive-Compulsive Disorder therapy, Parkinson Disease therapy, Stochastic Processes, Subthalamic Nucleus physiopathology, Treatment Outcome, Algorithms, Deep Brain Stimulation instrumentation, Models, Neurological, Signal-To-Noise Ratio
Abstract

Advances in the field of closed-loop neuromodulation call for analysis and modeling approaches capable of confronting challenges related to the complex neuronal response to stimulation and the presence of strong internal and measurement noise in neural recordings. Here we elaborate on the algorithmic aspects of a noise-resistant closed-loop subthalamic nucleus deep brain stimulation system for advanced Parkinson's disease and treatment-refractory obsessive-compulsive disorder, ensuring remarkable performance in terms of both efficiency and selectivity of stimulation, as well as in terms of computational speed. First, we propose an efficient method drawn from dynamical systems theory, for the reliable assessment of significant nonlinear coupling between beta and high-frequency subthalamic neuronal activity, as a biomarker for feedback control. Further, we present a model-based strategy through which optimal parameters of stimulation for minimum energy desynchronizing control of neuronal activity are being identified. The strategy integrates stochastic modeling and derivative-free optimization of neural dynamics based on quadratic modeling. On the basis of numerical simulations, we demonstrate the potential of the presented modeling approach to identify, at a relatively low computational cost, stimulation settings potentially associated with a significantly higher degree of efficiency and selectivity compared with stimulation settings determined post-operatively. Our data reinforce the hypothesis that model-based control strategies are crucial for the design of novel stimulation protocols at the backstage of clinical applications.

Published
2017
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22. Relationship between vagal tone, cortisol, TNF-alpha, epinephrine and negative affects in Crohn's disease and irritable bowel syndrome.

Author

Pellissier S, Dantzer C, Mondillon L, Trocme C, Gauchez AS, Ducros V, Mathieu N, Toussaint B, Fournier A, Canini F, and Bonaz B

Subjects
Adolescent, Adult, Case-Control Studies, Cluster Analysis, Crohn Disease blood, Crohn Disease metabolism, Female, Heart Rate, Humans, Hydrocortisone blood, Interleukin-6 blood, Irritable Bowel Syndrome blood, Irritable Bowel Syndrome metabolism, Male, Middle Aged, Norepinephrine blood, Saliva metabolism, Young Adult, Crohn Disease physiopathology, Epinephrine blood, Hydrocortisone metabolism, Irritable Bowel Syndrome physiopathology, Tumor Necrosis Factor-alpha blood, Vagus Nerve physiopathology
Abstract

Crohn's disease (CD) and irritable bowel syndrome (IBS) involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls). The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients). The day prior to the experiment, salivary cortisol was measured at 8:00 AM and 10:00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI) and depressive symptoms (CES-D). After 30 min of rest, ECG was recorded for heart rate variability (HRV) analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu) as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r =  -0.48; p<0.05) was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r =  -0.39; p<0.05). No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology) in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases.

Published
2014
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