Selective dentate gyrus disruption causes memory impairment at the early stage of experimental multiple sclerosis.

Autor: Planche V; INSERM, U1215, Neurocentre Magendie, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France; CHU de Clermont-Ferrand, F-63000 Clermont-Ferrand, France. Electronic address: planche.vincent@gmail.com., Panatier A; INSERM, U1215, Neurocentre Magendie, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France., Hiba B; Univ. Bordeaux, F-33000 Bordeaux, France; CNRS UMR 5287, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, F-33000 Bordeaux, France., Ducourneau EG; INSERM, U1215, Neurocentre Magendie, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France., Raffard G; Univ. Bordeaux, F-33000 Bordeaux, France; CNRS UMR 5536, Centre de Résonance Magnétique des Systèmes Biologiques, F-33000 Bordeaux, France., Dubourdieu N; INSERM, U1215, Neurocentre Magendie, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France., Maitre M; INSERM, U1215, Neurocentre Magendie, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France., Lesté-Lasserre T; INSERM, U1215, Neurocentre Magendie, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France., Brochet B; INSERM, U1215, Neurocentre Magendie, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France; CHU de Bordeaux, F-33000 Bordeaux, France., Dousset V; INSERM, U1215, Neurocentre Magendie, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France; CHU de Bordeaux, F-33000 Bordeaux, France., Desmedt A; INSERM, U1215, Neurocentre Magendie, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France., Oliet SH; INSERM, U1215, Neurocentre Magendie, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France., Tourdias T; INSERM, U1215, Neurocentre Magendie, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France; CHU de Bordeaux, F-33000 Bordeaux, France.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2017 Feb; Vol. 60, pp. 240-254. Date of Electronic Publication: 2016 Nov 12.
DOI: 10.1016/j.bbi.2016.11.010
Abstrakt: 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 minocycline 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.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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