TrpV1 receptor activation rescues neuronal function and network gamma oscillations from Aß-induced impairment in mouse hippocampus in vitro.
Elife
; 72018 11 12.
Article
em En
| MEDLINE
| ID: mdl-30417826
ABSTRACT
Amyloid-ß peptide (Aß) forms plaques in Alzheimer's disease (AD) and is responsible for early cognitive deficits in AD patients. Advancing cognitive decline is accompanied by progressive impairment of cognition-relevant EEG patterns such as gamma oscillations. The endocannabinoid anandamide, a TrpV1-receptor agonist, reverses hippocampal damage and memory impairment in rodents and protects neurons from Aß-induced cytotoxic effects. Here, we investigate a restorative role of TrpV1-receptor activation against Aß-induced degradation of hippocampal neuron function and gamma oscillations. We found that the TrpV1-receptor agonist capsaicin rescues Aß-induced degradation of hippocampal gamma oscillations by reversing both the desynchronization of AP firing in CA3 pyramidal cells and the shift in excitatory/inhibitory current balance. This rescue effect is TrpV1-receptor-dependent since it was absent in TrpV1 knockout mice or in the presence of the TrpV1-receptor antagonist capsazepine. Our findings provide novel insight into the network mechanisms underlying cognitive decline in AD and suggest TrpV1 activation as a novel therapeutic target.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Potenciais de Ação
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Capsaicina
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Células Piramidais
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Canais de Cátion TRPV
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Região CA3 Hipocampal
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Ritmo Gama
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Elife
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Suécia