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Your search keyword '"Sylvie Gory-Fauré"' showing total 9 results
Start Over Author "Sylvie Gory-Fauré" Topic 0303 health sciences
9 results on '"Sylvie Gory-Fauré"'

1. Impaired α-tubulin re-tyrosination leads to synaptic dysfunction and is a feature of Alzheimer’s disease

Author

Soleilhac J, Maria Elena Pero, Annie Andrieux, Julie Brocard, Francesca Bartolini, Sylvie Gory-Fauré, Di Cara B, Payet F, Parato J, Marie-Jo Moutin, Qu X, Atul Kumar, Christophe Bosc, Delagrange P, Charlotte Corrao, Leticia Peris, Yves Goldberg, Blanca Ramírez M, Falivelli G, José L. Martínez-Hernández, Fabien Lanté, Alain Buisson, Andrew Sproul, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Columbia University Medical Center (CUMC), Columbia University [New York], University of Naples Federico II, Institut de Recherches SERVIER (IRS), University of Naples Federico II = Università degli studi di Napoli Federico II, and Moutin, Marie-Jo

Subjects
0303 health sciences, biology, Chemistry, [SDV]Life Sciences [q-bio], Neurodegeneration, Neurotransmission, medicine.disease, Cell biology, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Tubulin, Microtubule, Detyrosination, Synaptic plasticity, medicine, biology.protein, Spine injury, Tyrosine, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

SUMMARYIn neurons, dynamic microtubules play regulatory roles in neurotransmission and synaptic plasticity. While stable microtubules contain detyrosinated tubulin, dynamic microtubules are composed of tyrosinated tubulin, suggesting that the tubulin tyrosination/detyrosination (Tyr/deTyr) cycle modulates microtubule dynamics and synaptic function. In the Tyr/deTyr cycle, the C-terminal tyrosine of α-tubulin is re-added by tubulin-tyrosine-ligase (TTL). Here we show that TTL+/− mice exhibit decreased tyrosinated microtubules, synaptic plasticity and memory deficits, and that reduced TTL expression is a feature of sporadic and familial Alzheimer’s disease (AD), with human APPV717I neurons having less dynamic microtubules. We find that spines visited by dynamic microtubules are more resistant to Amyloidβ1-42 and that TTL, by promoting microtubule entry into spines, prevents Aβ1-42-induced spine pruning. Our results demonstrate that the Tyr/deTyr cycle regulates synaptic plasticity, is protective against spine injury, and that tubulin re-tyrosination is lost in AD, providing evidence that a defective Tyr/deTyr cycle may contribute to neurodegeneration.

Published
2021

2. 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
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3. MAP6 dosage controls cognitive abilities

Author

Mohamed Saoud, Marie-Françoise Suaud-Chagny, Annie Andrieux, Jacques Brocard, Julien Volle, Jerome Brunelin, Sylvie Gory-Fauré, Schizophrenies Débutantes et Résistantes : de la Physiopathologie à la Thérapeutique, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, INSERM U836, équipe 1, Physiopathologie du cytosquelette, 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), Centre Hospitalier le Vinatier [Bron], Groupe Physiopathologie du Cytosquelette (GPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-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)-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), Région Rhône-Alpes France ('Cluster 11: Age-Handicap-Vieillissement'), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and 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)-Grenoble Institut des Neurosciences (GIN)

Subjects
Male, behavioural phenotype, Heterozygote, medicine.medical_specialty, Psychosis, Mice, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Animals, Allele, Amphetamine, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Maternal deprivation, Behavior, Animal, neurodevelopment, business.industry, Maternal Deprivation, animal model, Cognitive disorder, behavioral phenotype, Wild type, Regular Article, Heterozygote advantage, medicine.disease, Mice, Inbred C57BL, schizophrenia, Disease Models, Animal, Psychiatry and Mental health, Phenotype, Endocrinology, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, gene x environment interaction, Gene-Environment Interaction, Cognition Disorders, business, Microtubule-Associated Proteins, Neuroscience, Locomotion, 030217 neurology & neurosurgery, microtubule, medicine.drug
Abstract

International audience; Background: STOP/MAP6 null (KO) mice recapitulate behavioral abnormalities related to positive and negative symptoms and cognitive deficits of schizophrenia. Here, we investigated whether decreased expression of STOP/MAP6 proteins in heterozygous mice (only one allele expressed) would result in abnormal behavior related to those displayed by STOP null mice. Methods : Using a comprehensive test battery, we investigated the behavioral phenotype of STOP heterozygous (Het) mice compared with STOP KO and wild type (WT) mice on animals raised either in standard conditions (controls) or submitted to maternal deprivation. Results : Control Het mice displayed prominent deficits in social interaction and learning, resembling KO mice. In contrast, they exhibited short-lasting locomotor hyperreactivity to acute mild stress and no impaired locomotor response to amphetamine, much like WT mice. Additionally, perinatal stress deteriorated Het mouse phenotype by exacerbating alterations related to positive symptoms such as their locomotor reactivity to acute mild stress and psychostimulant challenge. Conclusion : Results show that the dosage of susceptibility genes modulates their putative phenotypic contribution and that STOP expression has a high penetrance on cognitive abilities. Hence, STOP Het mice might be useful to investigate cognitive defects related to those observed in mental diseases and ultimately might be a valuable experimental model to evaluate preventive treatments.

Published
2012
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4. Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy

Author

Veerle Janssens, Sylvie Gory-Fauré, Saadi Khochbin, Eloi Bahembera, Matthieu Rousset, Michel De Waard, Florian Lesage, Caroline Lambrecht, Abir Tadmouri, Maud Barbado, Karin Pernet-Gallay, Shigeki Kiyonaka, Ricardo E. Dolmetsch, Annie Andrieux, Michel Ronjat, Yasuo Mori, Sylvain Baulande, Seishiro Sawamura, Christophe Arnoult, Katell Fablet, Takafumi Miki, Karin Sadoul, and Satoshi Akiyama

Subjects
Regulation of gene expression, 0303 health sciences, General Immunology and Microbiology, biology, General Neuroscience, Repressor, Promoter, CACNB4, Molecular biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Histone H3, 0302 clinical medicine, Gene expression, biology.protein, Molecular Biology, Transcription factor, 030217 neurology & neurosurgery, 030304 developmental biology, Histone binding
Abstract

Calcium current through voltage-gated calcium channels (VGCC) controls gene expression. Here, we describe a novel signalling pathway in which the VGCC Cacnb4 subunit directly couples neuronal excitability to transcription. Electrical activity induces Cacnb4 association to Ppp2r5d, a regulatory subunit of PP2A phosphatase, followed by (i) nuclear translocation of Cacnb4/Ppp2r5d/PP2A, (ii) association with the tyrosine hydroxylase (TH) gene promoter through the nuclear transcription factor thyroid hormone receptor alpha (TRα), and (iii) histone binding through association of Cacnb4 with HP1γ concomitantly with Ser(10) histone H3 dephosphorylation by PP2A. This signalling cascade leads to TH gene repression by Cacnb4 and is controlled by the state of interaction between the SH3 and guanylate kinase (GK) modules of Cacnb4. The human R482X CACNB4 mutation, responsible for a form of juvenile myoclonic epilepsy, prevents association with Ppp2r5 and nuclear targeting of the complex by altering Cacnb4 conformation. These findings demonstrate that an intact VGCC subunit acts as a repressor recruiting platform to control neuronal gene expression.

Published
2012
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5. Neuronal Architectures with Axo-dendritic Polarity above Silicon Nanowires

Author

Sophie Roth, Sylvie Gory-Fauré, Catherine Villard, Mariano Bisbal, Ghislain Bugnicourt, Jacques Brocard, INSERM U836, équipe 1, Physiopathologie du cytosquelette, 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)-Institut Néel (NEEL), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), Groupe Physiopathologie du Cytosquelette (GPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-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)-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 Néel (NEEL), 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), Thermodynamique et biophysique des petits systèmes (NEEL - TPS), Institut Néel (NEEL), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), Nanoscience Foundation, Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Grenoble Institut des Neurosciences (GIN), Thermodynamique et biophysique des petits systèmes (TPS), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), and Andrieux, Annie

Subjects
Silicon, MESH: Axons, Materials science, MESH: Microscopy, Electron, Scanning, Polarity (physics), [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], MESH: Neurons, Nanowire, 02 engineering and technology, Cellular level, MESH: Dendrites, Signal, Biomaterials, Mice, 03 medical and health sciences, Animals, Nanotechnology, Automatic gain control, MESH: Animals, General Materials Science, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Silicon nanowires, MESH: Mice, MESH: Nanotechnology, Cells, Cultured, 030304 developmental biology, Neurons, MESH: Silicon, 0303 health sciences, [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Nanowires, business.industry, Dendrites, General Chemistry, 021001 nanoscience & nanotechnology, Axons, nervous system, MESH: Nanowires, Microscopy, Electron, Scanning, Optoelectronics, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 0210 nano-technology, business, MESH: Cells, Cultured, Biotechnology
Abstract

International audience; An approach is developped to gain control over the polarity of neuronal networks at the cellular level by physically constraining cell development by the use of micropatterns. It is demonstrated that the position and path of individual axons, the cell extension that propagates the neuron output signal, can be chosen with a success rate higher than 85%. This allows the design of small living computational blocks above silicon nanowires.

Published
2012
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6. Neuronal transport defects of the MAP6 KO mouse - a model of schizophrenia - and alleviation by Epothilone D treatment, as observed using MEMRI

Author

Sylvain Bohic, Annie Andrieux, Yasmina Saoudi, Emmanuel L. Barbier, Alexia Daoust, Jean-Christophe Deloulme, Clément Debacker, Sylvie Gory-Fauré, 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), European Synchrotron Radiation Facility (ESRF)-Grenoble Institut des Neurosciences (GIN), INSERM U836, équipe 1, Physiopathologie du cytosquelette, 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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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)-Bruker Biospin MRI, Bruker Biospin MRI-Bruker Biospin MRI, ANR-10-BLAN-1202,CBioS,Fonctions cellulaires des protéines STOP : vers une compréhension fonctionnelle et moléculaire du rôle des microtubules dans la transmission synaptique et l'organisation neuronale(2010), European Project, Andrieux, Annie, BLANC - Fonctions cellulaires des protéines STOP : vers une compréhension fonctionnelle et moléculaire du rôle des microtubules dans la transmission synaptique et l'organisation neuronale - - CBioS2010 - ANR-10-BLAN-1202 - BLANC - VALID, Région Rhône-Alpes - Cluster HVN, and INCOMING

Subjects
medicine.medical_specialty, Cognitive Neuroscience, Contrast Media, MEMRI, Neurotransmission, Somatosensory system, Synaptic Transmission, 03 medical and health sciences, Mice, 0302 clinical medicine, In vivo, Internal medicine, medicine, Animals, Humans, MAP6, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuronal transport, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Manganese, medicine.diagnostic_test, Chemistry, Magnetic resonance imaging, Somatosensory Cortex, Magnetic Resonance Imaging, Tubulin Modulators, 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, Treatment Outcome, Neurology, Epothilones, Synaptic plasticity, Axoplasmic transport, Schizophrenia, Epothilone D, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, Microtubule-Associated Proteins, 030217 neurology & neurosurgery, Neuronal tract
Abstract

International audience; The MAP6 (microtubule-associated protein 6) KO mouse is a microtubule-deficient model of schizophrenia that exhibits severe behavioral disorders that are associated with synaptic plasticity anomalies. These defects are alleviated not only by neuroleptics, which are the gold standard molecules for the treatment of schizophrenia, but also by Epothilone D (Epo D), which is a microtubule-stabilizing molecule. To compare the neuronal transport between MAP6 KO and wild-type mice and to measure the effect of Epo D treatment on neuronal transport in KO mice, MnCl2 was injected in the primary somatosensory cortex. Then, using manganese-enhanced magnetic resonance imaging (MEMRI), we followed the propagation of Mn(2+) through axonal tracts and brain regions that are connected to the somatosensory cortex. In MAP6 KO mice, the measure of the MRI relative signal intensity over 24h revealed that the Mn(2+) transport rate was affected with a stronger effect on long-range and polysynaptic connections than in short-range and monosynaptic tracts. The chronic treatment of MAP6 KO mice with Epo D strongly increased Mn(2+) propagation within both mono- and polysynaptic connections. Our results clearly indicate an in vivo deficit in neuronal Mn(2+) transport in KO MAP6 mice, which might be due to both axonal transport defects and synaptic transmission impairments. Epo D treatment alleviated the axonal transport defects, and this improvement most likely contributes to the positive effect of Epo D on behavioral defects in KO MAP6 mice.

Published
2014
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7. How morphological constraints affect axonal polarity in mouse neurons

Author

Sophie Roth, Catherine Villard, Sylvie Gory-Fauré, Mariano Bisbal, Yasmina Saoudi, Annie Andrieux, Ghislain Bugnicourt, Jacques Brocard, INSERM U836, équipe 1, Physiopathologie du cytosquelette, 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)-Institut Néel (NEEL), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), 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), 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)-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)-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 Néel (NEEL), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), Thermodynamique et biophysique des petits systèmes (TPS), Institut Néel (NEEL), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Nanoscience Foundation, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), 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)-Grenoble Institut des Neurosciences (GIN), Thermodynamique et biophysique des petits systèmes (NEEL - TPS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), and Andrieux, Annie

Subjects
MESH: Hippocampus, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cell, MESH: Neurons, lcsh:Medicine, Hippocampal formation, Hippocampus, MESH: Centrosome, Mice, chemistry.chemical_compound, 0302 clinical medicine, Cell polarity, Biomechanics, Cytochalasin, MESH: Animals, Axon, lcsh:Science, Cells, Cultured, Neurons, 0303 health sciences, Multidisciplinary, [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Physics, Cell Polarity, Anatomy, Cell Motility, medicine.anatomical_structure, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Cell Polarity, Research Article, Biotechnology, MESH: Cells, Cultured, MESH: Axons, Neurite, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Biophysics, Biology, 03 medical and health sciences, Developmental Neuroscience, Microtubule, medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Mice, 030304 developmental biology, Centrosome, lcsh:R, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Axons, chemistry, nervous system, Cellular Neuroscience, lcsh:Q, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; Neuronal differentiation is under the tight control of both biochemical and physical information arising from neighboring cells and micro-environment. Here we wished to assay how external geometrical constraints applied to the cell body and/or the neurites of hippocampal neurons may modulate axonal polarization in vitro. Through the use of a panel of non-specific poly-L-lysine micropatterns, we manipulated the neuronal shape. By applying geometrical constraints on the cell body we provided evidence that centrosome location was not predictive of axonal polarization but rather follows axonal fate. When the geometrical constraints were applied to the neurites trajectories we demonstrated that axonal specification was inhibited by curved lines. Altogether these results indicated that intrinsic mechanical tensions occur during neuritic growth and that maximal tension was developed by the axon and expressed on straight trajectories. The strong inhibitory effect of curved lines on axon specification was further demonstrated by their ability to prevent formation of multiple axons normally induced by cytochalasin or taxol treatments. Finally we provided evidence that microtubules were involved in the tension-mediated axonal polarization, acting as curvature sensors during neuronal differentiation. Thus, biomechanics coupled to physical constraints might be the first level of regulation during neuronal development, primary to biochemical and guidance regulations.

Published
2012
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8. Microtubule stabilizer ameliorates synaptic function and behavior in a mouse model for schizophrenia

Author

Mélina Bégou, Gerhard Höfle, Didier Job, Marie-Françoise Suaud-Chagny, Sylvie Gory-Fauré, Pekka Kujala, Annie Schweitzer, Philippe Brun, Paul A. Salin, Bastien Pachoud, Annie Andrieux, Organisation Fonctionnelle du Cytosquelette, 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)-IFR27, Physio-pathologie des réseaux neuronaux du cycle veille-sommeil, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut Fédératif des Neurosciences de Lyon (IFNL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Centre Hospitalier le Vinatier [Bron]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The Netherlands Cancer Institute, German Research Center for Biotechnology, and Andrieux, Annie

Subjects
Male, MESH: Hippocampus, MESH: Neurons, Hippocampus, Synaptic Transmission, MESH: Mice, Knockout, Mice, 0302 clinical medicine, MESH: Behavior, Animal, MESH: Animals, MAP6, MESH: Neuronal Plasticity, Maternal Behavior, Cells, Cultured, Mice, Knockout, Neurons, 0303 health sciences, Mice, Inbred BALB C, Neuronal Plasticity, Behavior, Animal, MESH: Electric Stimulation, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Tubulin Modulators, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Exploratory Behavior, Microtubule-Associated Proteins, medicine.drug, MESH: Cells, Cultured, MESH: Mice, Inbred BALB C, Biology, Synaptic vesicle, 03 medical and health sciences, Glutamatergic, Dopamine, MESH: Tubulin Modulators, medicine, MESH: Synaptic Transmission, Animals, MESH: Epothilones, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Excitatory Postsynaptic Potentials, MESH: Mice, Biological Psychiatry, 030304 developmental biology, Excitatory Postsynaptic Potentials, Actin cytoskeleton, Electric Stimulation, MESH: Male, MESH: Schizophrenia, Disease Models, Animal, MESH: Microtubule-Associated Proteins, Synaptic fatigue, Epothilones, MESH: Maternal Behavior, Synaptic plasticity, Exploratory Behavior, Schizophrenia, MESH: Disease Models, Animal, Neuroscience, MESH: Female, 030217 neurology & neurosurgery
Abstract

International audience; BACKGROUND: Recent data suggest that cytoskeletal defects may play a role in schizophrenia. We previously imitated features of schizophrenia in an animal model by disrupting gene coding for a microtubule-associated protein called STOP. STOP-null mice display synaptic defects in glutamatergic neurons, hyper-dopaminergy, and severe behavioral disorders. Synaptic and behavioral deficits are amended by neuroleptic treatment in STOP-null mice, providing an attractive model to test new antipsychotic agents. We examined the effects of a taxol-related microtubule stabilizer, epothilone D. METHODS: Mice were treated either with vehicle alone or with epothilone D. Treatment effects on synaptic function were assessed using electron-microscopy quantification of synaptic vesicle pools and electrophysiology in the CA1 region of the hippocampus. Dopamine transmission was investigated using electrochemical assays. Behavior was principally assessed using tests of maternal skills. RESULTS: In STOP-null mice, treatment with epothilone D increased synaptic vesicle pools, ameliorated both short- and long-term forms of synaptic plasticity in glutamatergic neurons, and had a dramatic beneficial effect on mouse behavior. CONCLUSIONS: A microtubule stabilizer can have a beneficial effect on synaptic function and behavior, suggesting new possibilities for treatment of schizophrenia.

Published
2006
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9. Phosphorylation of microtubule-associated protein STOP by calmodulin kinase II

Author

Laurent Blanchoin, Paul A. Salin, Fabrice Dufour, Christophe Bosc, Leticia Peris, Anne Fourest-Lieuvin, Didier Job, Julie Baratier, Annie Andrieux, Jacques Brocard, Sylvie Gory-Fauré, Organisation Fonctionnelle du Cytosquelette, 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)-IFR27, Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Physio-pathologie des réseaux neuronaux du cycle veille-sommeil, Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
multifunctional enzyme, actin binding, Microtubule-associated protein, microtubule stabilization, Biology, Biochemistry, Hippocampus, Microtubules, 03 medical and health sciences, Mice, 0302 clinical medicine, STOP protein, Calmodulin, Microtubule, Ca2+/calmodulin-dependent protein kinase, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MAP6, Phosphorylation, Cytoskeleton, Molecular Biology, mouse, 030304 developmental biology, Neurons, 0303 health sciences, synaptic plasticity, Brain, cytoskeleton, Cell Biology, calmodulin kinase, neuron, Actins, Cell biology, Protein Transport, medicine.anatomical_structure, Microscopy, Fluorescence, Synaptic plasticity, Calcium-Calmodulin-Dependent Protein Kinases, Synapses, Neuron, mammalia, microtubule associated protein, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Microtubule-Associated Proteins, 030217 neurology & neurosurgery
Abstract

STOP proteins are microtubule-associated, calmodulin-regulated proteins responsible for the high degree of stabilization displayed by neuronal microtubules. STOP suppression in mice induces synaptic defects affecting both short and long term synaptic plasticity in hippocampal neurons. Interestingly, STOP has been identified as a component of synaptic structures in neurons, despite the absence of microtubules in nerve terminals, indicating the existence of mechanisms able to induce a translocation of STOP from microtubules to synaptic compartments. Here we have tested STOP phosphorylation as a candidate mechanism for STOP relocalization. We show that, both in vitro and in vivo, STOP is phosphorylated by the multifunctional enzyme calcium/calmodulin-dependent protein kinase II (CaMKII), which is a key enzyme for synaptic plasticity. This phosphorylation occurs on at least two independent sites. Phosphorylated forms of STOP do not bind microtubules in vitro and do not co-localize with microtubules in cultured differentiating neurons. Instead, phosphorylated STOP co-localizes with actin assemblies along neurites or at branching points. Correlatively, we find that STOP binds to actin in vitro. Finally, in differentiated neurons, phosphorylated STOP co-localizes with clusters of synaptic proteins, whereas unphosphorylated STOP does not. Thus, STOP phosphorylation by CaMKII may promote STOP translocation from microtubules to synaptic compartments where it may interact with actin, which could be important for STOP function in synaptic plasticity.

Published
2006
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