Riluzole ameliorates soluble Aß1-42-induced impairments in spatial memory by modulating the glutamatergic/GABAergic balance in the dentate gyrus.
Prog Neuropsychopharmacol Biol Psychiatry
; 108: 110077, 2021 06 08.
Article
em En
| MEDLINE
| ID: mdl-32818535
ABSTRACT
Soluble amyloid beta (Aß) is believed to contribute to cognitive deficits in the early stages of Alzheimer's disease (AD). Increased soluble Aß1-42 in the hippocampus is closely correlated with spatial learning and memory deficits in AD. Riluzole (RLZ), an FDA-approved drug for amyotrophic lateral sclerosis (ALS), has beneficial effects for AD. However, the mechanism underlying the effects remains unclear. In this study, its neuroprotective effect against soluble Aß1-42-induced spatial cognitive deficits in rats was assessed. We found that intrahippocampal injection of soluble Aß1-42 impaired spatial cognitive function and suppressed long-term potentiation (LTP) of the DG region, which was relevant to soluble Aß1-42-induced shift of the hippocampal excitation/inhibition balance toward excitation. Interestingly, RLZ ameliorated Aß1-42-induced behavioral and LTP impairments through rescuing the soluble Aß1-42-induced excitation/inhibition imbalance. RLZ attenuated Aß1-42-mediated facilitation of excitatory synaptic transmission by facilitating glutamate reuptake and decreasing presynaptic glutamate release. Meanwhile, RLZ attenuated the suppression of inhibitory synaptic transmission caused by Aß1-42 by potentiating postsynaptic GABA receptor function. These results suggest that RLZ exerts a neuroprotective effect against soluble Aß1-42-related spatial cognitive deficits through rescuing the excitation/inhibition imbalance, and it could be a potential therapy for AD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Peptídeos beta-Amiloides
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Receptores de GABA
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Antagonistas de Aminoácidos Excitatórios
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Giro Denteado
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Riluzol
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Memória Espacial
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Prog Neuropsychopharmacol Biol Psychiatry
Ano de publicação:
2021
Tipo de documento:
Article