Search

Your search keyword '"Cyril Laurent"' showing total 30 results
Start Over Author "Cyril Laurent"
30 results on '"Cyril Laurent"'

1. Central activation of the fatty acid sensor GPR120 suppresses microglia reactivity and alleviates sickness- and anxiety-like behaviors

Author

Shingo Nakajima, Geneviève Demers, Arturo Israel Machuca-Parra, Zahra Dashtehei Pour, Diane Bairamian, Khalil Bouyakdan, Alexandre Fisette, Anita Kabahizi, Josephine Robb, Demetra Rodaros, Cyril Laurent, Guillaume Ferreira, Nathalie Arbour, Thierry Alquier, and Stephanie Fulton

Subjects
Free fatty acid receptor, Ffar4, Endotoxemia, Nucleus accumbens, Anxiety, Sickness behaviors, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract G protein-coupled receptor 120 (GPR120, Ffar4) is a sensor for long-chain fatty acids including omega-3 polyunsaturated fatty acids (n-3 PUFAs) known for beneficial effects on inflammation, metabolism, and mood. GPR120 mediates the anti-inflammatory and insulin-sensitizing effects of n-3 PUFAs in peripheral tissues. The aim of this study was to determine the impact of GPR120 stimulation on microglial reactivity, neuroinflammation and sickness- and anxiety-like behaviors by acute proinflammatory insults. We found GPR120 mRNA to be enriched in both murine and human microglia, and in situ hybridization revealed GPR120 expression in microglia of the nucleus accumbens (NAc) in mice. In a manner similar to or exceeding n-3 PUFAs, GPR120 agonism (Compound A, CpdA) strongly attenuated lipopolysaccharide (LPS)-induced proinflammatory marker expression in primary mouse microglia, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and inhibited nuclear factor-ĸB translocation to the nucleus. Central administration of CpdA to adult mice blunted LPS-induced hypolocomotion and anxiety-like behavior and reduced TNF-α, IL-1β and IBA-1 (microglia marker) mRNA in the NAc, a brain region modulating anxiety and motivation and implicated in neuroinflammation-induced mood deficits. GPR120 agonist pre-treatment attenuated NAc microglia reactivity and alleviated sickness-like behaviors elicited by central injection TNF-α and IL-1β. These findings suggest that microglial GPR120 contributes to neuroimmune regulation and behavioral changes in response to acute infection and elevated brain cytokines. GPR120 may participate in the protective action of n-3 PUFAs at the neural and behavioral level and offers potential as treatment target for neuroinflammatory conditions.

Published
2023
Full Text
View/download PDF

2. New piperazine multi-effect drugs prevent neurofibrillary degeneration and amyloid deposition, and preserve memory in animal models of Alzheimer's disease

Author

Nicolas Sergeant, Valérie Vingtdeux, Sabiha Eddarkaoui, Marion Gay, Caroline Evrard, Nicolas Le Fur, Cyril Laurent, Raphaelle Caillierez, Hélène Obriot, Paul-Emmanuel Larchanché, Amaury Farce, Mathilde Coevoet, Pascal Carato, Mostafa Kouach, Amandine Descat, Patrick Dallemagne, Valérie Buée-Scherrer, David Blum, Malika Hamdane, Luc Buée, and Patricia Melnyk

Subjects
Alzheimer's disease, Amyloid, Microtubule-associated protein tau, Multi-effect drugs, Neurofibrillary tangles, Tauopathies, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Alzheimer's Disease is a devastating dementing disease involving amyloid deposits, neurofibrillary tangles, progressive and irreversible cognitive impairment. Today, only symptomatic drugs are available and therapeutic treatments, possibly acting at a multiscale level, are thus urgently needed. To that purpose, we designed multi-effects compounds by synthesizing drug candidates derived by substituting a novel N,N′-disubstituted piperazine anti-amyloid scaffold and adding acetylcholinesterase inhibition property. Two compounds were synthesized and evaluated. The most promising hybrid molecule reduces both the amyloid pathology and the Tau pathology as well as the memory impairments in a preclinical model of Alzheimer's disease. In vitro also, the compound reduces the phosphorylation of Tau and inhibits the release of Aβ peptides while preserving the processing of other metabolites of the amyloid precursor protein.We synthetized and tested the first drug capable of ameliorating both the amyloid and Tau pathology in animal models of AD as well as preventing the major brain lesions and associated memory impairments. This work paves the way for future compound medicines against both Alzheimer's-related brain lesions development and the associated cognitive impairments.

Published
2019
Full Text
View/download PDF

3. The IL‐27/IL‐27R axis is altered in CD4+ and CD8+ T lymphocytes from multiple sclerosis patients

Author

Marie‐Laure Clénet, Cyril Laurent, Florent Lemaitre, Negar Farzam‐kia, Olivier Tastet, Odile Devergne, Boaz Lahav, Marc Girard, Pierre Duquette, Alexandre Prat, Catherine Larochelle, and Nathalie Arbour

Subjects
cytokines, IL‐12, neuroimmunology, PD‐L1, STAT signalling, T cells, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Objectives Pro‐ and anti‐inflammatory properties have been attributed to interleukin‐27 (IL‐27). Nevertheless, the impact of this cytokine on chronic inflammatory diseases such as multiple sclerosis (MS) remains ill‐defined. We investigated the biology of IL‐27 and its specific receptor IL‐27Rα in MS patients. Methods Levels of IL‐27 and its natural antagonist (IL‐27‐Rα) were measured by ELISA in biological fluids. CD4+ and CD8+ T lymphocytes were isolated from untreated relapsing–remitting MS patients and healthy donors. Transcriptome‐wide analysis compared T‐cell subsets stimulated or not with IL‐27. Expression of the IL‐27Rα, key immune factors, STAT phosphorylation and cytokine production was assessed by flow cytometry. Results We observed elevated levels of IL‐27 in the serum and cerebrospinal fluid of MS patients compared with controls. Moreover, we show that specific IL‐27‐mediated effects on T lymphocytes are reduced in MS patients including the induction of PD‐L1. IL‐27‐triggered STAT3 signalling pathway is enhanced in CD4+ and CD8+ T lymphocytes from MS patients. Elevated IL‐27Rα levels in serum from MS patients are sufficient to impair the capacity of IL‐27 to act on immune cells. We demonstrate that shedding of IL‐27Rα by activated CD4+ T lymphocytes from MS patients contributes to the increased IL‐27Rα peripheral levels and consequently can dampen the IL‐27 responsiveness. Conclusion Our work identifies several mechanisms that are altered in the IL‐27/IL‐27R axis in MS patients, especially in T lymphocytes. Our results underline the importance of characterising the biology of cytokines in human patients prior to design new therapeutics.

Published
2021
Full Text
View/download PDF

4. Mammalian Brain Ca2+ Channel Activity Transplanted into Xenopus laevis Oocytes

Author

Matthieu Rousset, Sandrine Humez, Cyril Laurent, Luc Buée, David Blum, Thierry Cens, Michel Vignes, and Pierre Charnet

Subjects
membrane microtransplantation, voltage clamp, CaV2 Ca2+ channels, channelopathies, Chemical technology, TP1-1185, Chemical engineering, TP155-156
Abstract

Several mutations on neuronal voltage-gated Ca2+ channels (VGCC) have been shown to cause neurological disorders and contribute to the initiation of epileptic seizures, migraines, or cerebellar degeneration. Analysis of the functional consequences of these mutations mainly uses heterologously expressed mutated channels or transgenic mice which mimic these pathologies, since direct electrophysiological approaches on brain samples are not easily feasible. We demonstrate that mammalian voltage-gated Ca2+ channels from membrane preparation can be microtransplanted into Xenopus oocytes and can conserve their activity. This method, originally described to study the alteration of GABA receptors in human brain samples, allows the recording of the activity of membrane receptors and channels with their native post-translational processing, membrane environment, and regulatory subunits. The use of hippocampal, cerebellar, or cardiac membrane preparation displayed different efficacy for transplanted Ca2+ channel activity. This technique, now extended to the recording of Ca2+ channel activity, may therefore be useful in order to analyze the calcium signature of membrane preparations from unfixed human brain samples or normal and transgenic mice.

Published
2022
Full Text
View/download PDF

5. Tau and neuroinflammation: What impact for Alzheimer's Disease and Tauopathies?

Author

Cyril Laurent, Luc Buée, and David Blum

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Alzheimer's Disease (AD) is a chronic neurodegenerative disorder and the most common type of dementia (60–80% of cases). In 2016, nearly 44 million people were affected by AD or related dementia. AD is characterized by progressive neuronal damages leading to subtle and latter obvious decline in cognitive functions including symptoms such as memory loss or confusion, which ultimately require full-time medical care. Its neuropathology is defined by the extracellular accumulation of amyloid-β (Aβ) peptide into amyloid plaques, and intraneuronal neurofibrillary tangles (NFT) consisting of aggregated hyper- and abnormal phosphorylation of tau protein. The latter, identified also as Tau pathology, is observed in a broad spectrum of neurological diseases commonly referred to as “Tauopathies”. Besides these lesions, sustained neuroinflammatory processes occur, involving notably micro- and astro-glial activation, which contribute to disease progression. Recent findings from genome wide association studies further support an instrumental role of neuroinflammation. While the interconnections existing between this innate immune response and the amyloid pathogenesis are widely characterized and described as complex, elaborated and evolving, only few studies focused on Tau pathology. An adaptive immune response takes place conjointly during the disease course, as indicated by the presence of vascular and parenchymal T-cell in AD patients' brain. The underlying mechanisms of this infiltration and its consequences with regards to Tau pathology remain understudied so far. In the present review, we highlight the interplays existing between Tau pathology and the innate/adaptive immune responses. Keywords: Alzheimer's disease, Tau, Inflammation, Glia, Astrocytes, Microglia

Published
2018
Full Text
View/download PDF

6. NKG2D and Its Ligand MULT1 Contribute to Disease Progression in a Mouse Model of Multiple Sclerosis

Author

Laurine Legroux, Ana Carmena Moratalla, Cyril Laurent, Gabrielle Deblois, Sandrine L. Verstraeten, and Nathalie Arbour

Subjects
T lymphocytes, central nervous system, autoimmune disease, neuroinflammation, NK cell lectin-like receptor subfamily, Immunologic diseases. Allergy, RC581-607
Abstract

NKG2D is an activating receptor expressed on the surface of immune cells including subsets of T lymphocytes. NKG2D binds multiple ligands (NKG2DL) whose expression are differentially triggered in a cell type and stress specific manner. The NKG2D-NKG2DL interaction has been involved in autoimmune disorders but its role in animal models of multiple sclerosis (MS) remains incompletely resolved. Here we show that NKG2D and its ligand MULT1 contribute to the pathobiology of experimental autoimmune encephalomyelitis (EAE). MULT1 protein levels are increased in the central nervous system (CNS) at EAE disease peak; soluble MULT1 is elevated in the cerebrospinal fluid of both active and passive EAE. We establish that such soluble MULT1 enhances effector functions (e.g., IFNγ production) of activated CD8 T lymphocytes from wild type but not from NKG2D-deficient (Klrk1−/−) mice in vitro. The adoptive transfer of activated T lymphocytes from wild type donors induced a significantly reduced EAE disease in Klrk1−/− compared to wild type (Klrk1+/+) recipients. Characterization of T lymphocytes infiltrating the CNS of recipient mice shows that donor (CD45.1) rather than endogenous (CD45.2) CD4 T cells are the main producers of key cytokines (IFNγ, GM-CSF). In contrast, infiltrating CD8 T lymphocytes include mainly endogenous (CD45.2) cells exhibiting effector properties (NKG2D, granzyme B and IFNγ). Our data support the notion that endogenous CD8 T cells contribute to passive EAE pathobiology in a NKG2D-dependent manner. Collectively, our results point to the deleterious role of NKG2D and its MULT1 in the pathobiology of a MS mouse model.

Published
2019
Full Text
View/download PDF

7. CD4+ Regulatory T Lymphocytes Prevent Impaired Cerebral Blood Flow in Angiotensin II‐Induced Hypertension

Author

M. Florencia Iulita, Sonia Duchemin, Diane Vallerand, Tlili Barhoumi, Fernando Alvarez, Roman Istomine, Cyril Laurent, Jessica Youwakim, Pierre Paradis, Nathalie Arbour, Ciriaco A. Piccirillo, Ernesto L. Schiffrin, and Hélène Girouard

Subjects
angiotensin, cerebral blood flow, inflammation, interleukin‐10, lymphocyte, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Immune cells are key regulators of the vascular inflammatory response characteristic of hypertension. In hypertensive rodents, regulatory T lymphocytes (Treg, CD4+CD25+) prevented vascular injury, cardiac damage, and endothelial dysfunction of mesenteric arteries. Whether Treg modulate the cerebrovascular damage induced by hypertension is unknown. Methods and Results C57BL/6 mice were perfused with angiotensin II (Ang II; 1000 ng/kg per minute) for 14 days and adoptive transfer of 3×105 CD4+CD25+ T cells was performed via 2 intravenous injections. Control mice received a sham surgery and PBS. Treg prevented Ang II‐induced neurovascular uncoupling (P

Published
2019
Full Text
View/download PDF

8. Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology

Author

Karim Belarbi, Sylvie Burnouf, Francisco-Jose Fernandez-Gomez, Cyril Laurent, Sophie Lestavel, Martin Figeac, Audrey Sultan, Laetitia Troquier, Antoine Leboucher, Raphaëlle Caillierez, Marie-Eve Grosjean, Dominique Demeyer, Hélène Obriot, Ingrid Brion, Bérangère Barbot, Marie-Christine Galas, Bart Staels, Sandrine Humez, Nicolas Sergeant, Susanna Schraen-Maschke, Anne Muhr-Tailleux, Malika Hamdane, Luc Buée, and David Blum

Subjects
Alzheimer's disease, Exercise, Tauopathies, THY-Tau22, Transgenic model, NPC1, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Tau pathology is encountered in many neurodegenerative disorders known as tauopathies, including Alzheimer's disease. Physical activity is a lifestyle factor affecting processes crucial for memory and synaptic plasticity. Whether long-term voluntary exercise has an impact on Tau pathology and its pathophysiological consequences is currently unknown. To address this question, we investigated the effects of long-term voluntary exercise in the THY-Tau22 transgenic model of Alzheimer's disease-like Tau pathology, characterized by the progressive development of Tau pathology, cholinergic alterations and subsequent memory impairments. Three-month-old THY-Tau22 mice and wild-type littermates were assigned to standard housing or housing supplemented with a running wheel. After 9 months of exercise, mice were evaluated for memory performance and examined for hippocampal Tau pathology, cholinergic defects, inflammation and genes related to cholesterol metabolism. Exercise prevented memory alterations in THY-Tau22 mice. This was accompanied by a decrease in hippocampal Tau pathology and a prevention of the loss of expression of choline acetyltransferase within the medial septum. Whereas the expression of most cholesterol-related genes remained unchanged in the hippocampus of running THY-Tau22 mice, we observed a significant upregulation in mRNA levels of NPC1 and NPC2, genes involved in cholesterol trafficking from the lysosomes. Our data support the view that long-term voluntary physical exercise is an effective strategy capable of mitigating Tau pathology and its pathophysiological consequences.

Published
2011
Full Text
View/download PDF

9. Mammalian Brain Ca

Author

Matthieu, Rousset, Sandrine, Humez, Cyril, Laurent, Luc, Buée, David, Blum, Thierry, Cens, Michel, Vignes, and Pierre, Charnet

Abstract

Several mutations on neuronal voltage-gated Ca

Published
2022

10. The IL‐27/IL‐27R axis is altered in CD4 + and CD8 + T lymphocytes from multiple sclerosis patients

Author

Marie-Laure Clénet, Nathalie Arbour, Pierre Duquette, Marc Girard, Alexandre Prat, Florent Lemaître, Odile Devergne, Negar Farzam-Kia, Cyril Laurent, Olivier Tastet, Catherine Larochelle, Boaz Lahav, Université de Montréal (UdeM), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de l'Université de Montréal (CHUM), Centre d'Immunologie et des Maladies Infectieuses (CIMI), and Gestionnaire, Hal Sorbonne Université

Subjects
lcsh:Immunologic diseases. Allergy, 0301 basic medicine, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Immunology, T cells, IL‐12, neuroimmunology, 03 medical and health sciences, 0302 clinical medicine, Immune system, PD-L1, medicine, Immunology and Allergy, Receptor, General Nursing, biology, business.industry, Multiple sclerosis, Original Articles, medicine.disease, cytokines, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Cytokine, Neuroimmunology, PD‐L1, Interleukin 12, biology.protein, Original Article, lcsh:RC581-607, business, STAT signalling, CD8, 030215 immunology
Abstract

Objectives Pro‐ and anti‐inflammatory properties have been attributed to interleukin‐27 (IL‐27). Nevertheless, the impact of this cytokine on chronic inflammatory diseases such as multiple sclerosis (MS) remains ill‐defined. We investigated the biology of IL‐27 and its specific receptor IL‐27Rα in MS patients. Methods Levels of IL‐27 and its natural antagonist (IL‐27‐Rα) were measured by ELISA in biological fluids. CD4+ and CD8+ T lymphocytes were isolated from untreated relapsing–remitting MS patients and healthy donors. Transcriptome‐wide analysis compared T‐cell subsets stimulated or not with IL‐27. Expression of the IL‐27Rα, key immune factors, STAT phosphorylation and cytokine production was assessed by flow cytometry. Results We observed elevated levels of IL‐27 in the serum and cerebrospinal fluid of MS patients compared with controls. Moreover, we show that specific IL‐27‐mediated effects on T lymphocytes are reduced in MS patients including the induction of PD‐L1. IL‐27‐triggered STAT3 signalling pathway is enhanced in CD4+ and CD8+ T lymphocytes from MS patients. Elevated IL‐27Rα levels in serum from MS patients are sufficient to impair the capacity of IL‐27 to act on immune cells. We demonstrate that shedding of IL‐27Rα by activated CD4+ T lymphocytes from MS patients contributes to the increased IL‐27Rα peripheral levels and consequently can dampen the IL‐27 responsiveness. Conclusion Our work identifies several mechanisms that are altered in the IL‐27/IL‐27R axis in MS patients, especially in T lymphocytes. Our results underline the importance of characterising the biology of cytokines in human patients prior to design new therapeutics., T lymphocytes play a central role in the pathobiology of chronic inflammatory diseases including multiple sclerosis (MS). We identified perturbations in the IL‐27/IL‐27R pathway in MS patients; IL‐27 triggers higher STAT3p response in T lymphocytes from MS vs. controls and induces PD‐L1 less efficiently on T cells from MS patients. Moreover, elevated IL‐27Rα levels in serum from MS patients, shed from activated CD4 T lymphocytes, are sufficient to impair the capacity of IL‐27 to act on immune cells.

Published
2021

11. Hyperexcitability and seizures in the THY-Tau22 mouse model of tauopathy

Author

Cyril Laurent, Luc Buée, Marie Basquin, Sandrine Parrot, Victoria Gomez-Murcia, David Blum, Ursula S. Sandau, Barbara Ferry, Detlev Boison, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Excellence Laboratory LabEx DISTALZ, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Rutgers University System (Rutgers), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Ferry, Barbara

Subjects
0301 basic medicine, Genetically modified mouse, Aging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Mice, Transgenic, tau Proteins, Adenosine kinase, Electroencephalography, Article, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Alzheimer Disease, Seizures, medicine, Animals, EEG, Pentylenetetrazol, medicine.diagnostic_test, biology, Seizure threshold, business.industry, General Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, THY-Tau22, Alzheimer's disease, medicine.disease, Astrogliosis, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Tauopathies, biology.protein, Pentylenetetrazole, Neurology (clinical), Tauopathy, Geriatrics and Gerontology, Tau, business, Neuroscience, 030217 neurology & neurosurgery, Developmental Biology, medicine.drug
Abstract

International audience; Epileptic seizures constitute a significant comorbidity of Alzheimer's disease (AD), which are recapitulated in transgenic mouse models of amyloidogenesis. Here, we sought to evaluate the potential role of tau pathology regarding seizure occurrence. To this end, we performed intra-hippocampal electroencephalogram (EEG) recordings and PTZ (pentylenetetrazol) seizure threshold tests in THY-Tau22 transgenic mice of AD-like tau pathology. We demonstrate that despite a lack of spontaneous epileptiform activity in Tau22 mice, the animals display increased PTZ-induced seizure susceptibility and mortality. The increased propensity for induced seizures in THY-Tau22 mutants correlates with astrogliosis and increased expression of adenosine kinase, consistent with increased network excitability. These data support an impact of tau pathology toward AD-associated seizures and suggest that tau pathology may contribute to seizure generation in AD independent of Aβ pathology.

Published
2020

12. Tau and neuroinflammation: What impact for Alzheimer's Disease and Tauopathies?

Author

Luc Buée, Cyril Laurent, David Blum, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Blum, David, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille

Subjects
0301 basic medicine, Amyloid, Tau protein, tau Proteins, Disease, Neuropathology, Adaptive Immunity, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, medicine, Humans, Dementia, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Phosphorylation, lcsh:QH301-705.5, Neuroinflammation, ComputingMilieux_MISCELLANEOUS, Inflammation, lcsh:R5-920, biology, business.industry, General Medicine, medicine.disease, Acquired immune system, Immunity, Innate, 3. Good health, 030104 developmental biology, Tauopathies, lcsh:Biology (General), Blood-Brain Barrier, biology.protein, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Alzheimer's disease, business, lcsh:Medicine (General), Neuroglia, Neuroscience, 030217 neurology & neurosurgery
Abstract

Alzheimer's Disease (AD) is a chronic neurodegenerative disorder and the most common type of dementia (60–80% of cases). In 2016, nearly 44 million people were affected by AD or related dementia. AD is characterized by progressive neuronal damages leading to subtle and latter obvious decline in cognitive functions including symptoms such as memory loss or confusion, which ultimately require full-time medical care. Its neuropathology is defined by the extracellular accumulation of amyloid-β (Aβ) peptide into amyloid plaques, and intraneuronal neurofibrillary tangles (NFT) consisting of aggregated hyper- and abnormal phosphorylation of tau protein. The latter, identified also as Tau pathology, is observed in a broad spectrum of neurological diseases commonly referred to as “Tauopathies”. Besides these lesions, sustained neuroinflammatory processes occur, involving notably micro- and astro-glial activation, which contribute to disease progression. Recent findings from genome wide association studies further support an instrumental role of neuroinflammation. While the interconnections existing between this innate immune response and the amyloid pathogenesis are widely characterized and described as complex, elaborated and evolving, only few studies focused on Tau pathology. An adaptive immune response takes place conjointly during the disease course, as indicated by the presence of vascular and parenchymal T-cell in AD patients' brain. The underlying mechanisms of this infiltration and its consequences with regards to Tau pathology remain understudied so far. In the present review, we highlight the interplays existing between Tau pathology and the innate/adaptive immune responses. Keywords: Alzheimer's disease, Tau, Inflammation, Glia, Astrocytes, Microglia

Published
2018

13. NKG2D and Its Ligand MULT1 Contribute to Disease Progression in a Mouse Model of Multiple Sclerosis

Author

Gabrielle Deblois, Ana Carmena Moratalla, Laurine Legroux, Sandrine L. Verstraeten, Cyril Laurent, and Nathalie Arbour

Subjects
lcsh:Immunologic diseases. Allergy, CD4-Positive T-Lymphocytes, 0301 basic medicine, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, Immunology, T lymphocytes, autoimmune disease, NK cell lectin-like receptor subfamily, chemical and pharmacologic phenomena, CD8-Positive T-Lymphocytes, neuroinflammation, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Animals, Cytotoxic T cell, Immunology and Allergy, Neuroinflammation, Original Research, Mice, Knockout, Chemistry, Histocompatibility Antigens Class I, Experimental autoimmune encephalomyelitis, Wild type, Brain, Membrane Proteins, central nervous system, medicine.disease, NKG2D, 3. Good health, Mice, Inbred C57BL, Granzyme B, Disease Models, Animal, 030104 developmental biology, Spinal Cord, NK Cell Lectin-Like Receptor Subfamily K, Disease Progression, lcsh:RC581-607, CD8, 030215 immunology
Abstract

NKG2D is an activating receptor expressed on the surface of immune cells including subsets of T lymphocytes. NKG2D binds multiple ligands (NKG2DL) whose expression are differentially triggered in a cell type and stress specific manner. The NKG2D-NKG2DL interaction has been involved in autoimmune disorders but its role in animal models of multiple sclerosis (MS) remains incompletely resolved. Here we show that NKG2D and its ligand MULT1 contribute to the pathobiology of experimental autoimmune encephalomyelitis (EAE). MULT1 protein levels are increased in the central nervous system (CNS) at EAE disease peak; soluble MULT1 is elevated in the cerebrospinal fluid of both active and passive EAE. We establish that such soluble MULT1 enhances effector functions (e.g. IFN production) of activated CD8 T lymphocytes from wild type but not from NKG2D-deficient (Klrk1-/-) mice in vitro. The adoptive transferred of activated T lymphocytes from wild type donors induced a significantly reduced EAE disease in Klrk1-/- compared to wild type (Klrk1+/+) recipients. Characterization of T lymphocytes infiltrating the CNS of recipient mice shows that donor (CD45.1) rather than endogenous (CD45.2) CD4 T cells are the main producers of key cytokines (IFN, GM-CSF). In contrast, infiltrating CD8 T lymphocytes include mainly endogenous (CD45.2) cells exhibiting effector properties (NKG2D, granzyme B and IFN). Our data support the notion that endogenous CD8 T cells contribute to passive EAE pathobiology in a NKG2D-dependent manner. Collectively, our results point to the deleterious role of NKG2D and its MULT1 in the pathobiology of a MS mouse model.

Published
2019
Full Text
View/download PDF

14. CD4+ Regulatory T Lymphocytes Prevent Impaired Cerebral Blood Flow in Angiotensin II‐Induced Hypertension

Author

Nathalie Arbour, Fernando Alvarez, Cyril Laurent, Roman Istomine, Hélène Girouard, Pierre Paradis, Ernesto L. Schiffrin, Sonia Duchemin, Jessica Youwakim, M. Florencia Iulita, Tlili Barhoumi, Diane Vallerand, and Ciriaco A. Piccirillo

Subjects
Male, Lymphocyte, cerebral blood flow, Inflammation, chemical and pharmacologic phenomena, Blood Pressure, lymphocyte, T-Lymphocytes, Regulatory, ACE/Angiotension Receptors/Renin Angiotensin System, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, interleukin‐10, Renin–angiotensin system, medicine, Laser-Doppler Flowmetry, Animals, IL-2 receptor, 030304 developmental biology, Original Research, 0303 health sciences, business.industry, Angiotensin II, hemic and immune systems, angiotensin, Immunity, Innate, 3. Good health, Mice, Inbred C57BL, Interleukin 10, Disease Models, Animal, medicine.anatomical_structure, Cerebral blood flow, Animal Models of Human Disease, inflammation, Cerebrovascular Circulation, Immunology, Hypertension, Endothelium/Vascular Type/Nitric Oxide, medicine.symptom, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract

Background Immune cells are key regulators of the vascular inflammatory response characteristic of hypertension. In hypertensive rodents, regulatory T lymphocytes (Treg, CD 4 + CD 25 + ) prevented vascular injury, cardiac damage, and endothelial dysfunction of mesenteric arteries. Whether Treg modulate the cerebrovascular damage induced by hypertension is unknown. Methods and Results C57 BL /6 mice were perfused with angiotensin II (Ang II ; 1000 ng/kg per minute) for 14 days and adoptive transfer of 3×10 5 CD 4 + CD 25 + T cells was performed via 2 intravenous injections. Control mice received a sham surgery and PBS . Treg prevented Ang II ‐induced neurovascular uncoupling ( P P II ‐induced neurovascular uncoupling ( P II ( P P P Conclusions Treg prevent impaired cerebrovascular responses in Ang II ‐induced hypertension. The neuroprotective effects of Treg involve the modulation of inflammation in the brain and periphery.

Published
2018

15. Interleukin-15 enhances proinflammatory T-cell responses in patients with MS and EAE

Author

Marc Girard, Ana Carmena Moratalla, Negar Farzam-Kia, Marie-Laure Clénet, Pierre Duquette, Alexandre Prat, Cyril Laurent, Nathalie Arbour, Gabrielle Deblois, and Catherine Larochelle

Subjects
Male, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, T-Lymphocytes, medicine.medical_treatment, T cell, Article, Proinflammatory cytokine, Flow cytometry, Mice, medicine, Animals, Humans, Interleukin-15, medicine.diagnostic_test, business.industry, Experimental autoimmune encephalomyelitis, medicine.disease, Mice, Inbred C57BL, Cytokine, medicine.anatomical_structure, Neurology, Interleukin 15, Immunology, Female, Tumor necrosis factor alpha, Neurology (clinical), business, CD8
Abstract

ObjectiveWe posit that interleukin-15 (IL-15) is a relevant contributor to MS pathobiology as this cytokine is elevated in the CNS and periphery of patients with MS. We aim to investigate (1) the impact of IL-15 on T lymphocytes from patients with MS and (2) the in vivo role of IL-15 using the experimental autoimmune encephalomyelitis (EAE) mouse model.MethodsWe compared the impact of IL-15 on T lymphocytes obtained from untreated patients with MS (relapsing-remitting, secondary progressive, and primary progressive) to cells from age/sex-matched healthy controls (HCs) using multiparametric flow cytometry and in vitro assays. We tested the effects of peripheral IL-15 administration after EAE disease onset in C57BL/6 mice.ResultsIL-15 triggered STAT5 signaling in an elevated proportion of T cells from patients with MS compared with HCs. This cytokine also enhanced the production of key proinflammatory cytokines (interferon γ, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-17, and tumor necrosis factor) by T cells from both MS and controls, but these effects were more robust for the production of IL-17 and GM-CSF in T-cell subsets from patients with MS. At the peak of EAE disease, the proportion of CD4+ and CD8+ T cells expressing CD122+, the key signaling IL-15 receptor chain, was enriched in the CNS compared with the spleen. Finally, peripheral administration of IL-15 into EAE mice after disease onset significantly aggravated clinical scores and increased the number of inflammatory CNS-infiltrating T cells long term after stopping IL-15 administration.ConclusionsOur results underscore that IL-15 contributes to the amplification of T-cell inflammatory properties after disease onset in both MS and EAE.

Published
2020

16. Tau et troubles cognitifs

Author

Cécile Delarasse, Elodie Martin, David Blum, Luc Buée, Guillaume Dorothée, Stéphane Hunot, and Cyril Laurent

Subjects
0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, business.industry, Medicine, General Medicine, business, 030217 neurology & neurosurgery, General Biochemistry, Genetics and Molecular Biology
Published
2017

17. [Tau and cognitive disorders: a role for T lymphocytes]

Author

Cyril, Laurent, Guillaume, Dorothée, Stéphane, Hunot, Elodie, Martin, Cécile, Delarasse, Luc, Buée, and David, Blum

Subjects
Alzheimer Disease, T-Lymphocytes, Animals, Brain, Cytokines, Humans, tau Proteins
Published
2017

18. The impact of IL-27 on human T cells is altered in multiple sclerosis patients

Author

Marie-Laure Clénet, Cyril Laurent, Odile Devergne, Pierre Duquette, Alexandre Prat, Catherine Larochelle, and Nathalie Arbour

Subjects
Immunology, Immunology and Allergy
Abstract

Interleukin-27 (IL-27) exhibits pro- and anti-inflammatory properties. Although this cytokine dampens the severity of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), whether IL 27 contributes to the pathobiology of MS remains unclear. We detected the IL-27 receptor (IL-27R) on brain-infiltrating T cells in MS tissues suggesting that they are susceptible to this cytokine. Notably, beneficial effects of MS immunomodulatory therapies are associated with IL-27 induction. We compared blood samples from untreated MS patients to healthy donors (HC) for i) serum levels of IL-27 and expression of IL-27R by T cells and ii) effects of IL-27 on phenotype and functions of T cells. Reduced proportions of CD4 T cells but greater percentages of CD8 T cells expressed IL-27R in MS patients compared to HC. IL-27 triggered phosphorylation of STAT1 (pSTAT1) and STAT3 (pSTAT3) in all T cell subsets; similar levels of pSTAT1 were induced in T cells from MS and HC. In contrast, increased proportions of CD4 and CD8 T cells exhibited pSTAT3 in response to IL-27 compared to cells from HC. Moreover, addition of IL-27 to activated T cells significantly decreased the percentages of GM-CSF or IL-17 producing CD4 and CD8 T cells from MS patients but had a minimal impact on HC’s cells. Finally, sera from MS patients contained elevated amounts of soluble IL-27 and IL-27Rα (a natural IL-27 antagonist) compared to HC. Our results reveal that IL-27 has an enhanced impact on T cells from MS patients, which could contribute to dampen key immune responses (e.g. GM-CSF, IL-17) associated with this inflammatory/autoimmune disease. However, elevated in vivo levels of its natural antagonist could hinder IL-27-mediated anti-inflammatory properties.

Published
2019

19. Detrimental Effects of Diet-Induced Obesity on τ Pathology Are Independent of Insulin Resistance in τ Transgenic Mice

Author

Dominique Demeyer, David Blum, Christophe Breton, Pascal Pigny, Raphaëlle Caillierez, Laetitia Troquier, Francisco-Jose Fernandez-Gomez, Malika Hamdane, Kadiombo Bantubungi, Luc Buée, Sabiha Eddarkaoui, Nadège Zommer, Anne Tailleux, Emmanuelle Vallez, Bart Staels, Antoine Leboucher, Sylvie Burnouf, Cyril Laurent, and Valérie Buée-Scherrer

Subjects
Genetically modified mouse, medicine.medical_specialty, Pathology, biology, Insulin Receptor Substrate Proteins, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, medicine.disease, Insulin receptor, Insulin resistance, Endocrinology, Downregulation and upregulation, Internal medicine, Immunology, Internal Medicine, medicine, biology.protein, Alzheimer's disease, Cognitive decline
Abstract

The τ pathology found in Alzheimer disease (AD) is crucial in cognitive decline. Midlife development of obesity, a major risk factor of insulin resistance and type 2 diabetes, increases the risk of dementia and AD later in life. The impact of obesity on AD risk has been suggested to be related to central insulin resistance, secondary to peripheral insulin resistance. The effects of diet-induced obesity (DIO) on τ pathology remain unknown. In this study, we evaluated effects of a high-fat diet, given at an early pathological stage, in the THY-Tau22 transgenic mouse model of progressive AD-like τ pathology. We found that early and progressive obesity potentiated spatial learning deficits as well as hippocampal τ pathology at a later stage. Surprisingly, THY-Tau22 mice did not exhibit peripheral insulin resistance. Further, pathological worsening occurred while hippocampal insulin signaling was upregulated. Together, our data demonstrate that DIO worsens τ phosphorylation and learning abilities in τ transgenic mice independently from peripheral/central insulin resistance.

Published
2013

20. Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of tauopathy

Author

Cécile Delarasse, Yuan Dong, Yann Monnet, Raphaëlle Caillierez, Susanna Schraen-Maschke, Luc Buée, Antoine Leboucher, Sylvie Burnouf, Nadège Zommer, Cyril Laurent, François-Pierre Légeron, Elodie Martin, Guillaume Dorothée, Stéphane Hunot, Nathalie Jouy, Dominique Demeyer, Kevin Carvalho, Emilie Faivre, Véronique Sazdovitch, David Blum, Marie Duchamp, Blum, David, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Unité de Virologie clinique et fondamentale (UVCF), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, STMicroelectronics [Rousset] (ST-ROUSSET), Physico-Chimie-Curie (PCC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Système immunitaire et neuroinflammation [CRSA], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
CD4-Positive T-Lymphocytes, 0301 basic medicine, CD3 Complex, T cells, Hippocampus, Mice, Transgenic, chemokines, CD8-Positive T-Lymphocytes, Hippocampal formation, Antibodies, neuroinflammation, Mice, 03 medical and health sciences, 0302 clinical medicine, mental disorders, medicine, Animals, Humans, Dementia, Cognitive Dysfunction, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cognitive decline, Neuroinflammation, ComputingMilieux_MISCELLANEOUS, Aged, Cerebral Cortex, Inflammation, tauopathy, Original Articles, Frontotemporal lobar degeneration, Middle Aged, medicine.disease, Pathophysiology, Mice, Inbred C57BL, Disease Models, Animal, frontotemporal lobar degeneration, 030104 developmental biology, Tauopathies, Immunology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Tauopathy, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract

The role of immune responses in the cognitive impairments associated with tauopathy is unclear. Laurent et al. identify a CD8+ T-cell infiltration in the hippocampus of THY-Tau22 transgenic mice. T-cell depletion reverses spatial memory deficits in these animals, supporting a role for hippocampal T-cell infiltration in tau-driven cognitive impairments., Alzheimer’s disease is characterized by the combined presence of amyloid plaques and tau pathology, the latter being correlated with the progression of clinical symptoms. Neuroinflammatory changes are thought to be major contributors to Alzheimer’s disease pathophysiology, even if their precise role still remains largely debated. Notably, to what extent immune responses contribute to cognitive impairments promoted by tau pathology remains poorly understood. To address this question, we took advantage of the THY-Tau22 mouse model that progressively develops hippocampal tau pathology paralleling cognitive deficits and reappraised the interrelationship between tau pathology and brain immune responses. In addition to conventional astroglial and microglial responses, we identified a CD8-positive T cell infiltration in the hippocampus of tau transgenic mice associated with an early chemokine response, notably involving CCL3. Interestingly, CD8-positive lymphocyte infiltration was also observed in the cortex of patients exhibiting frontemporal dementia with P301L tau mutation. To gain insights into the functional involvement of T cell infiltration in the pathophysiological development of tauopathy in THY-Tau22 mice, we chronically depleted T cells using anti-CD3 antibody. Such anti-CD3 treatment prevented hippocampal T cell infiltration in tau transgenic animals and reverted spatial memory deficits, in absence of tau pathology modulation. Altogether, these data support an instrumental role of hippocampal T cell infiltration in tau-driven pathophysiology and cognitive impairments in Alzheimer’s disease and other tauopathies.

Published
2016

21. Hippocampal BDNF Expression in a Tau Transgenic Mouse Model

Author

Malika Hamdane, Maxime Derisbourg, Sylvie Burnouf, Antoine Leboucher, Cyril Laurent, Dominique Demeyer, Karim Belarbi, Luc Buée, David Blum, and Laetitia Troquier

Subjects
Male, Genetically modified mouse, Amyloid, Transgene, Enzyme-Linked Immunosorbent Assay, Mice, Transgenic, tau Proteins, Biology, Hippocampal formation, Hippocampus, Mice, Western blot, Neurotrophic factors, medicine, Extracellular, Animals, Humans, RNA, Messenger, medicine.diagnostic_test, Brain-Derived Neurotrophic Factor, Age Factors, Up-Regulation, Mice, Inbred C57BL, Disease Models, Animal, Tauopathies, Neurology, Mutation, Neurology (clinical), Neuroscience, Intracellular
Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular accumulation of amyloid deposits and intracellular neurofibrillary tangles (NFT) composed of hyperphosphorylated Tau proteins. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor playing a critical role in hippocampal synaptic plasticity and memory and whose levels have been shown reduced in AD brains. While recent data support a pivotal role of β-amyloid peptides towards BDNF decrease, whether Tau pathology impacts on BDNF expression remains unknown so far. In the present study, we have evaluated this relationship using quantitative PCR, Western blot and ELISA in the THY-Tau22 transgenic strain, known to display a progressive development of both hippocampal AD-like Tau pathology and memory impairments. We observed that Tau pathology was not associated with down-regulation of BDNF at the protein and mRNA levels in this model, suggesting that the alteration of BDNF homeostasis observed in AD patients' brains might rather be ascribed to amyloid pathology.

Published
2012

22. Le site de référence du Partenariat européen d’innovation pour un vieillissement actif et en bonne santé MACVIA-LR (contre les maladies chroniques pour un vieillissement en bonne santé en Languedoc-Roussillon)

Author

Miren David, Ariane Sultan, Guillaume Pandraud, Benoît G. Bardy, Jacques Morel, Giacomo Cavalli, Sylvain Jacquemin, Christine Rolland, Cyril Breuker, Philippe Boulet, Gregoire Mercier, Stéphane Bouly, Valérie Bruguière, Gwen Mathieu, Marc Meissonnier, Hervé Tassery, Vincent Marmelat, Michel Dauzat, Hubert Blain, Gérard Dray, Cyril Laurent, Christine Viarouge-Reunier, Marie Virginie Calmels, François Rivier, Gérard Dupeyron, Gérard Bourrel, Jacquie Berthe, Philippe Domy, Béatrice Lognos, Martine Aoustin, Davide Caimmi, Michel Kaczorek, Mélanie Badin, Pierre Nicolas, Alain Le Quellec, Sylvie Boichot, Vincent Le Moing, C. Boegner, Jérôme Fernandes, Michel Amouyal, Matthieu Desplan, Jean Paul Cristol, T. Camuzat, Karima Bakhti, Jean Michel Verdier, Paule Adnet, Christophe Jorgensen, Denis Sablot, Jean Ribstein, Henriette Dhivert-Donnadieu, Céline Vergne-Richard, Emilie Porte, Christine Azevedo, Isabelle Quéré, Dominique Jakovenko, Marion Gellerat-Rogier, Michel Tanfin, Karen Ritchie, Flavia Oana Coroian, Bernard Guillot, Fabrice Nouvel, J. Pelissier, Anna Bedbrook, Daniel Laune, Jean-Luc Bourrain, Yves Marie Pers, Jean Luc Savy, Chantal Marion, Cherif Heroum, Marianna Danko, Grégoire Vergotte, Françoise Radier-Pontal, Jean Luc Pasquié, Olivier Bénézet, Bernard Combe, Sylvain Richard, Liliane Landreau, Valérie Cros, Isabelle Rédini-Martinez, Emilie Viollet, David Guiraud, François Roubille, Jérôme Froger, Bertrand Coulet, Laurent Journot, Marie Suzanne Léglise, Sylvie Arnavieilhe, Isabel Tavares, Samir Jaber, Olivier Jonquet, David Morquin, Philippe Van de Perre, Roland Sicard, Raphaël Chiron, Vincent Tribout, Pierre Senesse, Xavier Quantin, Jacques Touchon, Kevin Mandrick, Alain Uziel, Vincent Bouix, Marie Christine Picot, Philippe Augé, Martine Lapierre, Antoine Avignon, Eric Pastor, Pascal Demoly, Kjerstin Torre, Jacques Mercier, Jean-Marie Robine, Dominique Larrey, D. J. Costa, Grégory Ninot, Laurent Schifano, Baya Soua, Anne Wojtusciszyn, Jean-Christophe Gris, Didier Delignières, Florence Gressard, Marie Pierre Pasdelou, Fabienne Portejoie, Michel Mondain, Philippe Nérin, Olivier Hantkié, Xavier Bobia, Delphine Paccard, Pierre Géraud Claret, Maxime Villiet, Jacques Burille, Christian Hérisson, Guillaume Tallon, V. Attalin, Jean Emmanuel de la Coussaye, William Camu, Didier Hoa, Chokri Boubakri, Jacques Reynes, Michel Enjalbert, Pascal Kouyoumdjian, Anthony Gellis, Jean Marc Lussert, Jean Philippe Pin, Christian Bourquin, Jean-Marc Lemaitre, Rodolphe Bourret, Isabelle Laffont, Claudine Berr, Marie Christine Courrouy-Michel, Nicolas Giraudeau, Trias Asteriou, Catherine Leblond, Cyril Meunier, Sylvain Lehmann, M. Nogues, Denise Strubel, Raul Punta-Morales, Alain Makinson, Jacques Bringer, Stéphane Perrey, Nathalie Pinto, Yannick Stephan, Charles Fattal, Jean Marc Davy, Arnaud Bourdin, Emilie Royère, Arnaud Dupeyron, Claire Daien, François Vialla, Frédéric Viart, Joël Bockaert, Arnaud Yves Goucham, Pierre Aubas, Huei Yune Bonnin, Fares Gouzi, Véronique Carre, Nicolas Best, Jean Pierre Riso, Jérome Cottalorda, Max Villain, Philippe Dauenhauer, Patrick Messner, Amélie Matheron, Claude Jeandel, Roxana Taddei-Ologeanu, Bernard Alomène, Sylvie Albert, Stéphane Cade, Gérard Canovas, Pauline Coignard, Karine Patte, Sofiane Ramdani, Frédéric Abecassis, Maurice Hayot, Marc Ychou, Anne Laure Coupet, Nathalie Raffort, D. Heve, Philippe Gabrion, Pierre Mares, Pierre Labauge, Marie Pierre Battesti, Denis Mottet, Philippe Fraisse, Jean Bousquet, Jean Louis Pujol, Emilie Galano, Pierre Fesler, Vincent Dufour, Gregory Baptista, Pierre Louis Bernard, Mireille Fouletier, Pierre Dujol, Xavier Vasquez, Jean Paul Ortiz, Pierre Martin-Gousset, Philippe Courtet, Oude Engberink, Valérie Handweiler, S. Granier, Laurence Vian, Françoise Leclercq, Frédéric Cuisinier, Pierre Costa, Guillaume Cayla, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Département d'anesthésie-réanimation[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Department of Geriatrics - Efficiency and Deficiency Laboratory, Hadassah Hebrew University Medical Center [Jerusalem], IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT), Département de Biostatistiques, Agence Régionale de Santé Languedoc Roussillon (ARS), Institut de Recherche en Infectiologie de Montpellier (IRIM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Roche Pharma Research and Early Development [Basel] (pRED), F. Hoffmann-La Roche [Basel], Service de gynécologie-obstétrique, Mécanismes adaptatifs : des organismes aux communautés (MAOAC), Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF)-Muséum national d'Histoire naturelle (MNHN), Laboratoire de Géochimie Isotopique Environnementale (GIS) / Université de Nîmes (GIS), Université de Nîmes (UNIMES)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Genre (LARHRA GENRE), LAboratoire de Recherche Historique Rhône-Alpes - UMR5190 (LARHRA), Centre National de la Recherche Scientifique (CNRS)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Grenoble Alpes (UGA), Département de Médecine générale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Control of Artificial Movement and Intuitive Neuroprosthesis (CAMIN), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Département de médecine générale, Université de Montpellier (UM), Euromov (EuroMov), Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Laboratoire de Mathématiques Blaise Pascal (LMBP), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), CERFRANCE Nord Est - Ile de France, Réseau de Vigilance en Dermato-Allergologie - Groupe d'Etudes et de Recherches en DERmato-Allergologie (Revidal-Gerda), Réseau de Vigilance en Dermato-Allergologie (Revidal), Centre Mutualiste de Rééducation et de Réadaptation Fonctionnelles de KERPAPE [Ploemeur] (CMRRF), Centre Mutualiste de Rééducation et de Réadaptation Fonctionnelles de Kerpape, Laboratoire de Bioingénierie et NanoSciences (LBN), Institut de Génétique Moléculaire de Montpellier (IGMM), Dynamique des capacités humaines et des conduites de santé (EPSYLON), Université Montpellier 1 (UM1)-Université Paul-Valéry - Montpellier 3 (UM3)-Université de Montpellier (UM), Laboratory of Cardio-Vascular Physiology (LCVP), Université Montpellier 1 (UM1), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Rééducation et Réadaptation Neuro Orthopédique [Nîmes] (Pôle NACRRE), Hôpital Universitaire Carémeau [Nîmes], Centre Mutualiste de Réeducation Neurologique Propara (PROPARA), Languedoc Mutualité, Oc Santé Montpellier, Artificial movement and gait restoration (DEMAR), Unité de Rééducation Neurologique, Centre Hélio-Marin CHU Nîmes, Department de Dermatologie, Médecine physique et de réadaptation, Hôpital Lapeyronie [Montpellier] (CHU), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie Orthopédique, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Centre Bouffard-Vercelli, Laboratoire de Mécanique et Technologie (LMT), École normale supérieure - Cachan (ENS Cachan)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Plateforme de Protéomique Clinique, CHU Saint-Eloi, Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Université de Montpellier (UM), Département Conception et conduite des véhicules Aéronautiques et Spatiaux (DCAS), Institut Supérieur de l'Aéronautique et de l'Espace (ISAE-SUPAERO), Lab-STICC_TB_CID_TOMS, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de recherche souterrain de Meuse/Haute-Marne, Agence Nationale de gestion des Déchets Radioactifs, Aix-Marseille Université - Faculté des Sciences du Sport (AMU FSS), Aix Marseille Université (AMU), HORIBA Medical (HORIBA ABX SAS), HORIBA Scientific [France], Unité Mathématique, Informatique et Génome (MIG), Institut National de la Recherche Agronomique (INRA), Interactions, Corpus, Apprentissages, Représentations (ICAR), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique (CNRS), Unité clinique d'Immuno-Rhumatologie & Thérapeutique des maladies ostéo-articulaires, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS), UNICANCER - Institut régional du Cancer [Montpellier] (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Biocommunication en Cardio-Métabolique (BC2M), Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département d'oncologie médicale et digestive, Centre de cancérologie Val d'Aurelle, Complexité, Innovation, Activités Motrices et Sportives (CIAMS), Université d'Orléans (UO)-Université Paris-Sud - Paris 11 (UP11), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche et de Diagnostic sur le Sida (CeDreS), CHU Treichville, Interaction entre Systèmes Protéiques et Différenciation dans la Cellule Tumorale (ISPDCT), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Dynamiques du droit (DD), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Centre National de la Recherche Scientifique (CNRS), Centre de pharmacologie et innovation dans le diabète (CPID), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre National de la Recherche Scientifique (CNRS), Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] ( PhyMedExp ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), IMT - Mines Alès Ecole Mines - Télécom ( IMT - MINES ALES ), Agence Régionale de Santé Languedoc Roussillon ( ARS ), Institut de Recherche en Infectiologie de Montpellier ( IRIM ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ), Roche Pharma Research and Early Development [Basel] ( pRED ), Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Mécanismes adaptatifs : des organismes aux communautés ( MAOAC ), Muséum National d'Histoire Naturelle ( MNHN ) -Collège de France ( CdF ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Géochimie Isotopique Environnementale (GIS) / Université de Nîmes ( GIS ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Nîmes ( UNIMES ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon ( MACVIA-LR ), Université Montpellier 1 ( UM1 ) -World Health Organization ( WHO/OMS ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -European Innovation Partnership on Active and Healthy Ageing Reference Site, Agence Nationale de Sécurité Sanitaire, de l'Alimentation, de l'environnement et du Travail ( ANSES ), ANSES, Genre ( LARHRA GENRE ), LAboratoire de Recherche Historique Rhône-Alpes - UMR5190 ( LARHRA ), Centre National de la Recherche Scientifique ( CNRS ) -Université Jean Moulin - Lyon III-Université Lumière - Lyon 2 ( UL2 ) -École normale supérieure - Lyon ( ENS Lyon ) -Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Jean Moulin - Lyon III-Université Lumière - Lyon 2 ( UL2 ) -École normale supérieure - Lyon ( ENS Lyon ) -Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Grenoble Alpes ( UGA ), Université Montpellier 1 ( UM1 ), Artificial movement and gait restoration ( DEMAR ), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier ( LIRMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -Inria Sophia Antipolis - Méditerranée ( CRISAM ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ), Université de Montpellier ( UM ), Euromov ( EuroMov ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre Européen de Réalité Virtuelle ( CERV ), École Nationale d'Ingénieurs de Brest ( ENIB ), Laboratoire de Mathématiques Blaise Pascal ( LMBP ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ), Université Montpellier 1 ( UM1 ) -IFR76-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Réseau de Vigilance en Dermato-Allergologie - Groupe d'Etudes et de Recherches en DERmato-Allergologie ( Revidal-Gerda ), Réseau de Vigilance en Dermato-Allergologie ( Revidal ), Centre Mutualiste de Rééducation et de Réadaptation Fonctionnelles de KERPAPE [Ploemeur] ( CMRRF ), Laboratoire de Bioingénierie et NanoScience-UM, Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Dynamique des capacités humaines et des conduites de santé ( EPSYLON ), Université Paul-Valéry - Montpellier 3 ( UM3 ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Laboratory of Cardio-Vascular Physiology ( LCVP ), Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département de Rééducation et Réadaptation Neuro Orthopédique [Nîmes] ( Pôle NACRRE ), Centre Mutualiste de Réeducation Neurologique Propara ( PROPARA ), Hôpital Lapeyronie [Montpellier] ( CHU ), Institut de Génomique Fonctionnelle - Montpellier GenomiX ( IGF MGX ), Laboratoire de Mécanique et Technologie ( LMT ), École normale supérieure - Cachan ( ENS Cachan ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Saint-Eloi-Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Recherches Translationnelles sur le VIH et les maladies infectieuses ( TransVIHMI ), Université Montpellier 1 ( UM1 ) -Université Cheikh Anta Diop ( UCAD ) -Universtié Yaoundé 1 (Cameroun)-Université de Montpellier ( UM ), Département Conception et conduite des véhicules Aéronautiques et Spatiaux ( DCAS ), Institut Supérieur de l'Aéronautique et de l'Espace ( ISAE-SUPAERO ), Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance ( Lab-STICC ), École Nationale d'Ingénieurs de Brest ( ENIB ) -Université de Bretagne Sud ( UBS ) -Université de Brest ( UBO ) -Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Université européenne de Bretagne ( UEB ) -ENSTA Bretagne-Institut Mines-Télécom [Paris]-Centre National de la Recherche Scientifique ( CNRS ) -École Nationale d'Ingénieurs de Brest ( ENIB ) -Université de Bretagne Sud ( UBS ) -Université de Brest ( UBO ) -Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Université européenne de Bretagne ( UEB ) -ENSTA Bretagne-Institut Mines-Télécom [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Aix-Marseille Université - Faculté des Sciences du Sport ( AMU FSS ), Aix Marseille Université ( AMU ), HORIBA Medical ( HORIBA ABX SAS ), Unité Mathématique, Informatique et Génome ( MIG ), Institut National de la Recherche Agronomique ( INRA ), Interactions, Corpus, Apprentissages, Représentations ( ICAR ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Institut de Chimie des Substances Naturelles ( ICSN ), Centre National de la Recherche Scientifique ( CNRS ), UNICANCER - Institut régional du Cancer [Montpellier] ( ICM ), Efficience Déficience Motrice [Montpellier] ( EDM ), Centre de pharmacologie et innovation dans le diabète ( CPID ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Centre National de la Recherche Scientifique ( CNRS ), Complexité, Innovation, Activités Motrices et Sportives ( CIAMS ), Université Paris-Sud - Paris 11 ( UP11 ) -Université d'Orléans ( UO ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Montpellier 2 - Sciences et Techniques ( UM2 ) -IFR76-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de recherche et de Diagnostic sur le Sida ( CeDreS ), Interaction entre Systèmes Protéiques et Différenciation dans la Cellule Tumorale ( ISPDCT ), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique ( CNRS ), Dynamiques du droit ( DD ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7), École des hautes études en sciences sociales (EHESS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Génie Informatique et Ingénierie de Production (LGI2P), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Agence Régionale de la Santé (ARS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre Mendès France - Grenoble 2 (UPMF)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Inria Sophia Antipolis - Méditerranée (CRISAM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université Paul-Valéry - Montpellier 3 (UPVM)-Université de Montpellier (UM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Oc Santé [Montpellier], Interactive Digital Humans (IDH), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Service de Rhumatologie [CHRU Montpellier], École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut du Cancer de Montpellier (ICM), Université Paris-Sud - Paris 11 (UP11)-Université d'Orléans (UO), Centre de recherche et de Diagnostic sur le Sida [Abidjan, Côte d'Ivoire] (CeDreS), Centre Hospitalier Universitaire de Treichville [Abidjan, Côte d'Ivoire] (CHU de Treichville), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 1 (UM1), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1), Muséum national d'Histoire naturelle (MNHN)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), and CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Aging, [ SDV ] Life Sciences [q-bio], business.industry, [SDV]Life Sciences [q-bio], General Medicine, MESH: Accidental Falls, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Medicine, 030211 gastroenterology & hepatology, Accidental Falls, MESH: Aging, 030212 general & internal medicine, business, Humanities, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Le site de référence du Partenariat européen d'innovation pour un vieillissement actif et en bonne santé MACVIA-LR (contre les maladies chroniques pour un vieillissement en bonne santé en Languedoc-Roussillon)

Published
2015

23. Role of the Tau N-terminal region in microtubule stabilization revealed by new endogenous truncated forms

Author

Luc Buée, Coline Leghay, Maxime Derisbourg, Yann Verdier, Valérie Buée-Scherrer, Francisco-Jose Fernandez-Gomez, Sébastien Carrier, David Blum, Joëlle Vinh, Malika Hamdane, Nicolas Sergeant, Dominique Demeyer, Giovanni Chiappetta, Cyril Laurent, Spectrométrie de Masse Biologique et Protéomique (USR3149 / FRE2032) (SMBP), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Alzheimer & Tauopathies [JPArc], Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Neurobiologie et diversité cellulaire (NDC), Neuroendocrinologie et physiopathologie neuronale, Institut National de la Santé et de la Recherche Médicale (INSERM), Alzheimer & Tauopathies (Equipe 1), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, and Verdier, Yann

Subjects
Proteomics, [SDV]Life Sciences [q-bio], Cell, Endogeny, tau Proteins, Bioinformatics, Cleavage (embryo), Microtubule stabilization, Microtubules, Article, Cell Line, Microtubule, Alzheimer Disease, Tubulin, mental disorders, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Functional studies, Phosphorylation, Multidisciplinary, Chemistry, Brain, Acetylation, Human brain, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Nerve Degeneration, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Protein Processing, Post-Translational, Protein Binding
Abstract

Tau is a central player in Alzheimer's disease (AD) and relatedTauopathies, where it is found as aggregates in degenerating neurons. Abnormalpost-translational modifications, such as truncation, are likely involved in thepathological process. A major step forward in understanding the role of Tautruncation would be to identify the precise cleavage sites of the several truncatedTau fragments that are observed until now in AD brains, especially those truncatedat the N-terminus, which are less characterized than those truncated at theC-terminus. Here, we optimized a proteomics approach and succeeded in identifying anumber of new N-terminally truncated Tau species from the human brain. We initiatedcell-based functional studies by analyzing the biochemical characteristics of twoN-terminally truncated Tau species starting at residues Met11 and Gln124respectively. Our results show, interestingly, that the Gln124-Tau fragment displaysa stronger ability to bind and stabilize microtubules, suggesting that the TauN-terminal domain could play a direct role in the regulation of microtubulestabilization. Future studies based on our new N-terminally truncated-Tau speciesshould improve our knowledge of the role of truncation in Tau biology as well as inthe AD pathological process.

Published
2015

24. From epidemiology to pathophysiology: what about caffeine in Alzheimer’s disease?

Author

Sandrine Humez, Luísa V. Lopes, Detlev Boison, Joana E. Coelho, Vânia L. Batalha, Malika Hamdane, David Blum, Sylvie Burnouf, Vanessa Flaten, Ursula S. Sandau, Luc Buée, Cyril Laurent, and Repositório da Universidade de Lisboa

Subjects
medicine.medical_specialty, Epidemiology, Adenosinergic, Disease, Biology, Bioinformatics, Biochemistry, Article, Alzheimer Disease, Internal medicine, Caffeine, medicine, Dementia, Animals, Humans, Senile plaques, Pathological, Receptors, Purinergic P1, medicine.disease, Pathophysiology, 3. Good health, Endocrinology, Purinergic P1 Receptor Antagonists, Alzheimer's disease, Adenosine receptor A2A, Alzheimer’s disease
Abstract

© The Authors Journal compilation © 2014 Biochemical Society, AD (Alzheimer's disease) is the most prevalent form of dementia in the aged population. Definitive diagnosis of AD is based on the presence of senile plaques and neurofibrillary tangles that are identified in post-mortem brain specimens. A third pathological component is inflammation. AD results from multiple genetic and environmental risk factors. Among other factors, epidemiological studies report beneficial effects of caffeine, a non-selective antagonist of adenosine receptors. In the present review, we discuss the impact of caffeine and the adenosinergic system in AD pathology as well as consequences in terms of pathology and therapeutics., D.Bl. and L.B. are supported by France Alzheimer, La Ligue Européenne Contre la Maladie d’Alzheimer (LECMA)/Alzheimer Forschung Initiative, LabEx (excellence laboratory) DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease), Inserm, Centre National de la Recherche Scientifique (CNRS), Université Lille 2, Région Nord/Pas-de-Calais, Agence Nationale de la Recherche (ADORATAU), ERA-Net (ABeta-ID) and Fonds Unique Interministériel MEDIALZ. V.F. holds a grant from Inserm/Region Nord pas de Calais. C.L. holds a doctoral grant from Lille 2 University. D.Bo. is supported through grants from the National Institutes of Health [grant numbers NS065957, MH083973 and NS061844], the U.S. Department of the Army [grant number W81XWH-12-1-0283] and the Legacy Good Samaritan Foundation. L.V.L. is an FCT Investigator (iFCT). Her laboratory has support from Fritz-Thyssen Foundation, Bial and Fundação para a Ciência e a Tecnologia (FCT) (Portugal). D.B. is an Inserm investigator.

Published
2014

25. Les plateformes 'longévité' sur Nîmes Métropole

Author

Jamin, Frédéric, Cyril, Laurent, Laboratoire de Mécanique et Génie Civil (LMGC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Conception en structures (CS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut méditerranéen des métiers de la longévité (I2ML), and Institut méditerranéen des métiers de la longévité

Subjects
[SPI.GCIV]Engineering Sciences [physics]/Civil Engineering, innovations technologiques, vieillissement, longévité
Abstract

L'Institut Universitaire de Technologie de Nîmes a entrepris depuis mars 2012, en collaboration avec l'Institut Méditerranéen des Métiers de la Longévité, la conception et la réalisation d'une plateforme technique " logement témoin accessible " dont les trois objectifs principaux sont la formation initiale obligatoire des " futurs " professionnels du cadre bâti, la formation et la sensibilisation des acteurs du cadre bâti et la recherche appliquée omniprésente dans le cadre bâti sur le contraste visuel, d'une part, et pour le maintien à domicile des personnes âgées, d'autre part. Pour le premier objectif, il s'agit de répondre à la loi n°2005-102 du 11 février 2005 - Article 41-V précisant que les formations qui conduisent aux diplômes, titres et certifications préparant à des professions dont l'objet est la conception ou la réalisation de bâtiments doivent impérativement dispenser une formation sur l'accessibilité des personnes handicapées. Pour le second objectif, il s'agit de proposer une formation aux professionnels du cadre bâti car nous constatons que la réglementation sur l'accessibilité des personnes handicapées est souvent source de tension entre les concepteurs, les entrepreneurs tout corps d'état, les vérificateurs et les utilisateurs. Pour le troisième objectif, il s'agit de tester en amont les différents outils ou équipements en vue de les mettre en œuvre ensuite dans un Living Lab dont le principe consiste à mettre en situation réelle une ou plusieurs personnes dans les conditions d'utilisation d'un logement et, par le biais de l'observation, de tirer des leçons sur les pratiques quotidiennes de vie des occupants afin d'apporter une réponse technologique à leurs besoins ou à leurs exigences. Dans le cadre de cette recherche appliquée, nous souhaitons apporter notre contribution sur la domotique qui apparaît être un outil incontournable pour le maintien à domicile. Le département Génie Civil de l'IUT de Nîmes a dédié un espace de 49 m2 dans lequel le logement (figure 1) comprend deux entrées, un séjour de 16 m2, une cuisine (figure 2) d'environ 9 m2, une chambre d'environ 12 m2 et une salle d'eau / cabinet d'aisances de 8 m2. La perspective de pouvoir profiter d'équipements adaptés aux personnes handicapées au sens large du terme (déficiences motrice, sensorielle ou cognitive) permettra sans aucun doute aux étudiants et aux professionnels de mieux appréhender la notion de handicap et les problèmes quotidiens auxquels sont confrontés les personnes en situation de handicap mais également d'étudier de nouveaux procédés ergonomiques ou de développer des guides " de bonnes pratiques " en fonction du type de handicap. Au delà de la formation, ce logement permettra aussi de développer la recherche appliquée comme lieu de tests d'équipements domotiques et vitrine de savoir-faire en matière de domotique.

Published
2013

26. Beneficial effects of caffeine in a transgenic model of Alzheimer's disease-like tau pathology

Author

Antoine Leboucher, Christa E. Müller, David Blum, Marion Schneider, Sébastien Carrier, Maxime Derisbourg, Luc Buée, Malika Hamdane, Sabiha Eddarkaoui, Cyril Laurent, and Dominique Demeyer

Subjects
Genetically modified mouse, Male, Aging, medicine.medical_specialty, Hippocampus, Mice, Transgenic, tau Proteins, medicine.disease_cause, Proinflammatory cytokine, Transgenic Model, chemistry.chemical_compound, Alzheimer Disease, Internal medicine, Caffeine, medicine, Animals, Cognitive decline, Phosphorylation, Memory Disorders, General Neuroscience, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, chemistry, Proteolysis, Neurology (clinical), Tauopathy, Geriatrics and Gerontology, Psychology, Neuroscience, Oxidative stress, Developmental Biology
Abstract

Tau pathology found in Alzheimer's disease (AD) is crucial in cognitive decline. Epidemiologic evidences support that habitual caffeine intake prevents memory decline during aging and reduces the risk to develop Alzheimer's disease. So far, experimental studies addressed the impact of caffeine in models mimicking the amyloid pathology of AD. However, in vivo effects of caffeine in a model of AD-like tauopathy remain unknown. Here, we evaluated effects of chronic caffeine intake (0.3 g/L through drinking water), given at an early pathologic stage, in the THY-Tau22 transgenic mouse model of progressive AD-like tau pathology. We found that chronic caffeine intake prevents from the development of spatial memory deficits in tau mice. Improved memory was associated with reduced hippocampal tau phosphorylation and proteolytic fragments. Moreover, caffeine treatment mitigated several proinflammatory and oxidative stress markers found upregulated in the hippocampus of THY-Tau22 animals. Together, our data support that moderate caffeine intake is beneficial in a model of AD-like tau pathology, paving the way for future clinical evaluation in AD patients.

Published
2013

27. NMDA receptor dysfunction contributes to impaired brain-derived neurotrophic factor-induced facilitation of hippocampal synaptic transmission in a Tau transgenic model

Author

Anne Muhr-Tailleux, Malika Hamdane, Laetitia Troquier, Sabiha Eddarkaoui, Sandrine Humez, Patrizia Popoli, Karim Belarbi, Alberto Martire, David Blum, Marie-Eve Grosjean, Alain Buisson, Maxime Derisbourg, Antoine Leboucher, Cyril Laurent, Sylvie Burnouf, Nicolas Sergeant, Francisco J. Fernandez-Gomez, Dominique Demeyer, and Luc Buée

Subjects
Male, Aging, medicine.medical_specialty, Mice, Transgenic, tau Proteins, AMPA receptor, Tropomyosin receptor kinase B, Hippocampal formation, Neurotransmission, Biology, Hippocampus, Receptors, N-Methyl-D-Aspartate, Synaptic Transmission, 03 medical and health sciences, Mice, 0302 clinical medicine, Neurotrophic factors, Alzheimer Disease, medicine, Animals, Humans, Transgenes, Psychiatry, 030304 developmental biology, Brain-derived neurotrophic factor, 0303 health sciences, musculoskeletal, neural, and ocular physiology, Brain-Derived Neurotrophic Factor, Cell Biology, Mice, Inbred C57BL, Disease Models, Animal, nervous system, Synaptic plasticity, NMDA receptor, Neuroscience, 030217 neurology & neurosurgery
Abstract

While the spatiotemporal development of Tau pathology has been correlated with occurrence of cognitive deficits in Alzheimer's patients, mechanisms underlying these deficits remain unclear. Both brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor TrkB play a critical role in hippocampus-dependent synaptic plasticity and memory. When applied on hippocampal slices, BDNF is able to enhance AMPA receptor-dependent hippocampal basal synaptic transmission through a mechanism involving TrkB and N-methyl-d-Aspartate receptors (NMDAR). Using THY-Tau22 transgenic mice, we demonstrated that hippocampal Tau pathology is associated with loss of synaptic enhancement normally induced by exogenous BDNF. This defective response was concomitant to significant memory impairments. We show here that loss of BDNF response was due to impaired NMDAR function. Indeed, we observed a significant reduction of NMDA-induced field excitatory postsynaptic potential depression in the hippocampus of Tau mice together with a reduced phosphorylation of NR2B at the Y1472, known to be critical for NMDAR function. Interestingly, we found that both NR2B and Src, one of the NR2B main kinases, interact with Tau and are mislocalized to the insoluble protein fraction rich in pathological Tau species. Defective response to BDNF was thus likely related to abnormal interaction of Src and NR2B with Tau in THY-Tau22 animals. These are the first data demonstrating a relationship between Tau pathology and synaptic effects of BDNF and supporting a contribution of defective BDNF response and impaired NMDAR function to the cognitive deficits associated with Tauopathies.

Published
2012

28. Adenosine Receptors and Alzheimer’s Disease

Author

Vânia L. Batalha, David Blum, Luc Buée, Detlev Boison, Luísa V. Lopes, Cyril Laurent, Antoine Leboucher, Ursula S. Sandau, Florence Pasquier, and Malika Hamdane

Subjects
biology, Amyloid beta, business.industry, Tau protein, Neurofibrillary tangle, Adenosinergic, Purinergic signalling, medicine.disease, Adenosine, Astrogliosis, biology.protein, medicine, Senile plaques, business, Neuroscience, medicine.drug
Abstract

Alzheimer’s disease (AD) is the most prevalent form of dementia in the aged population. Definitive diagnosis of AD is based on the presence of senile plaques and neurofibrillary tangles that are identified in post-mortem brain specimens. The formation of these AD-specific lesions is attributed to the pathological accumulation of either extracellular amyloid beta (Aβ) peptide or intraneuronal hyperphosphorylated Tau protein. The AD brain is also characterized by astrogliosis and inflammation. Sporadic AD results from multiple genetic and environmental risk factors. Prospective, retrospective epidemiological studies and experimental findings have identified chronic caffeine consumption as a protective factor. Caffeine effects would essentially result from modulation of the adenosine system. In this frame, the present review aims to discuss the role of adenosinergic system and in particular involvement of the A2AR in AD pathology and associated cognitive impairments. We also discuss the apparent paradox in regards to A2AR blockade and the aforementioned protective effects versus the disruption of specific biochemical processes that influence hippocampal synaptic plasticity, BDNF/TrkB signaling and acetylcholine release, all being associated with AD physiopathology. As an alternative to targeting specific pathways a more effective option to treat AD may be achieved by utilizing novel treatment strategies that restore adenosine homeostasis in the diseased brain. Thus, prior to exploring the efficacy of A2AR blockade as a therapeutic option for AD, we conclude that a better understanding of adenosine signaling in AD is needed.

Published
2012

29. P3‐004: Voluntary exercise in THY‐Tau22 mice prevents tau pathology and its consequences

Author

Valérie Buée-Scherrer, Cyril Laurent, Raphaëlle Caillierez, Laetitia Troquier, Francisco-Jose Fernandez-Gomez, Malika Hamdane, Nicolas Sergeant, Karim Belarbi, David Blum, Antoine Leboucher, Sylvie Burnouf, and Luc Buée

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Tau pathology, Developmental Neuroscience, Epidemiology, business.industry, Health Policy, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience
Published
2011

30. Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology

Author

Audrey Sultan, Sandrine Humez, Cyril Laurent, David Blum, I. Brion, B. Barbot, Marie-Christine Galas, Dominique Demeyer, Marie-Eve Grosjean, Bart Staels, Malika Hamdane, Raphaëlle Caillierez, Laetitia Troquier, Anne Muhr-Tailleux, Francisco-Jose Fernandez-Gomez, Martin Figeac, Karim Belarbi, Susanna Schraen-Maschke, Hélène Obriot, Antoine Leboucher, Sylvie Burnouf, Nicolas Sergeant, Sophie Lestavel, and Luc Buée

Subjects
Genetically modified mouse, Male, Hippocampus, Physical exercise, Mice, Transgenic, tau Proteins, Hippocampal formation, lcsh:RC321-571, Transgenic model, Mice, Alzheimer Disease, Physical Conditioning, Animal, medicine, Animals, Humans, Exercise, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, THY-Tau22, Alzheimer's disease, medicine.disease, Choline acetyltransferase, Pathophysiology, NPC1, Exercise Therapy, Mice, Inbred C57BL, Disease Models, Animal, Neurology, Tauopathies, Cholinergic, Psychology, Neuroscience
Abstract

Tau pathology is encountered in many neurodegenerative disorders known as tauopathies, including Alzheimer's disease. Physical activity is a lifestyle factor affecting processes crucial for memory and synaptic plasticity. Whether long-term voluntary exercise has an impact on Tau pathology and its pathophysiological consequences is currently unknown. To address this question, we investigated the effects of long-term voluntary exercise in the THY-Tau22 transgenic model of Alzheimer's disease-like Tau pathology, characterized by the progressive development of Tau pathology, cholinergic alterations and subsequent memory impairments. Three-month-old THY-Tau22 mice and wild-type littermates were assigned to standard housing or housing supplemented with a running wheel. After 9 months of exercise, mice were evaluated for memory performance and examined for hippocampal Tau pathology, cholinergic defects, inflammation and genes related to cholesterol metabolism. Exercise prevented memory alterations in THY-Tau22 mice. This was accompanied by a decrease in hippocampal Tau pathology and a prevention of the loss of expression of choline acetyltransferase within the medial septum. Whereas the expression of most cholesterol-related genes remained unchanged in the hippocampus of running THY-Tau22 mice, we observed a significant upregulation in mRNA levels of NPC1 and NPC2, genes involved in cholesterol trafficking from the lysosomes. Our data support the view that long-term voluntary physical exercise is an effective strategy capable of mitigating Tau pathology and its pathophysiological consequences.

Published
2010

Catalog

Books, media, physical & digital resources
See catalog results