Selective dentate gyrus disruption causes memory impairment at the early stage of experimental multiple sclerosis
| Autor: | Eva-Gunnel Ducourneau, Aude Panatier, Marlène Maitre, Thierry Leste-Lasserre, Stéphane H. R. Oliet, Vincent Planche, Vincent Dousset, Thomas Tourdias, Gérard Raffard, Bruno Brochet, Bassem Hiba, Nadège Dubourdieu, Aline Desmedt |
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| Přispěvatelé: | Université de Bordeaux (UB), Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique des systèmes biologiques (CRMSB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Encephalomyelitis Autoimmune Experimental Multiple Sclerosis [SDV]Life Sciences [q-bio] Immunology Long-Term Potentiation Hippocampus Hippocampal formation Synaptic Transmission 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Medicine Memory impairment Animals Memory Disorders Endocrine and Autonomic Systems business.industry Multiple sclerosis Dentate gyrus Experimental autoimmune encephalomyelitis Long-term potentiation medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology nervous system Synaptic plasticity Dentate Gyrus Synapses Female Microglia business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Brain, Behavior, and Immunity Brain, Behavior, and Immunity, Elsevier, 2017, 60, pp.240-254. ⟨10.1016/j.bbi.2016.11.010⟩ |
| ISSN: | 0889-1591 1090-2139 |
| DOI: | 10.1016/j.bbi.2016.11.010⟩ |
| Popis: | International audience; Memory impairment is an early and disabling manifestation of multiple sclerosis whose anatomical and biological substrates are still poorly understood. We thus investigated whether memory impairment encountered at the early stage of the disease could be explained by a differential vulnerability of particular hippocampal subfields. By using experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, we identified that early memory impairment was associated with selective alteration of the dentate gyrus as pinpointed in vivo with diffusion-tensor-imaging (DTI). Neuromorphometric analyses and electrophysiological recordings confirmed dendritic degeneration, alteration in glutamatergic synaptic transmission and impaired long-term synaptic potentiation selectively in the dentate gyrus, but not in CA1, together with a more severe pattern of microglial activation in this subfield. Systemic injections of the microglial inhibitor minocycline prevented DTI, morphological, electrophysiological and behavioral impairments in EAE-mice. Furthermore, daily infusions of minocy-cline specifically within the dentate gyrus were sufficient to prevent memory impairment in EAE-mice while infusions of minocycline within CA1 were inefficient. We conclude that early memory impairment in EAE is due to a selective disruption of the dentate gyrus associated with microglia activation. These results open new pathophysiological, imaging, and therapeutic perspectives for memory impairment in multiple sclerosis. |
| Databáze: | OpenAIRE |
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