Inhibition of Histone Deacetylase Reinstates Hippocampus-Dependent Long-Term Synaptic Plasticity and Associative Memory in Sleep-Deprived Mice.
Cereb Cortex
; 30(7): 4169-4182, 2020 06 01.
Article
em En
| MEDLINE
| ID: mdl-32188968
ABSTRACT
Sleep plays an important role in the establishment of long-term memory; as such, lack of sleep severely impacts domains of our health including cognitive function. Epigenetic mechanisms regulate gene transcription and protein synthesis, playing a critical role in the modulation of long-term synaptic plasticity and memory. Recent evidences indicate that transcriptional dysregulation as a result of sleep deprivation (SD) may contribute to deficits in plasticity and memory function. The histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA), also known as Vorinostat, a clinically approved drug for human use, has been shown to ameliorate cognitive deficits in several neurological disease models. To further explore the therapeutic effect of SAHA, we have examined its potential role in improving the SD-mediated impairments in long-term plasticity, associative plasticity, and associative memory. Here we show that SAHA preserves long-term plasticity, associative plasticity, and associative memory in SD hippocampus. Furthermore, we find that SAHA prevents SD-mediated epigenetic changes by upregulating histone acetylation, hence preserving the ERK-cAMP-responsive element-binding protein (CREB)/CREB-binding protein-brain-derived neurotrophic factor pathway in the hippocampus. These data demonstrate that modifying epigenetic mechanisms via SAHA can prevent or reverse impairments in long-term plasticity and memory that result from sleep loss. Thus, SAHA could be a potential therapeutic agent in improving SD-related memory deficits.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Associação
/
Privação do Sono
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Potenciação de Longa Duração
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Inibidores de Histona Desacetilases
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Vorinostat
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Hipocampo
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Memória
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Cereb Cortex
Assunto da revista:
CEREBRO
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Singapura