Selective dentate gyrus disruption causes memory impairment at the early stage of experimental multiple sclerosis.
Brain Behav Immun
; 60: 240-254, 2017 Feb.
Article
em En
| MEDLINE
| ID: mdl-27847283
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Potenciação de Longa Duração
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Encefalomielite Autoimune Experimental
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Transtornos da Memória
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Esclerose Múltipla
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Brain Behav Immun
Assunto da revista:
ALERGIA E IMUNOLOGIA
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CEREBRO
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PSICOFISIOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article