NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors.
J Clin Invest
; 122(10): 3593-602, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22996661
ABSTRACT
The formation of a long-lasting memory requires a transcription-dependent consolidation period that converts a short-term memory into a long-term memory. Nuclear receptors compose a class of transcription factors that regulate diverse biological processes, and several nuclear receptors have been implicated in memory formation. Here, we examined the potential contribution of nuclear receptors to memory consolidation by measuring the expression of all 49 murine nuclear receptors after learning. We identified 13 nuclear receptors with increased expression after learning, including all 3 members of the Nr4a subfamily. These CREB-regulated Nr4a genes encode ligand-independent "orphan" nuclear receptors. We found that blocking NR4A activity in memory-supporting brain regions impaired long-term memory but did not impact short-term memory in mice. Further, expression of Nr4a genes increased following the memory-enhancing effects of histone deacetylase (HDAC) inhibitors. Blocking NR4A signaling interfered with the ability of HDAC inhibitors to enhance memory. These results demonstrate that the Nr4a gene family contributes to memory formation and is a promising target for improving cognitive function.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Nootrópicos
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Receptores Nucleares Órfãos
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Inibidores de Histona Desacetilases
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Memória de Longo Prazo
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Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article