The antidepressant action of 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid is mediated by phosphorylation of histone deacetylase 5
The Korean Journal of Physiology and Pharmacology
;
: 155-162, 2018.
Artigo
em Inglês
| WPRIM
| ID: wpr-728626
ABSTRACT
3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, produces rapid antidepressant-like effects in animal models of depression. However, the molecular mechanisms underlying these behavioral actions remain unknown. Here, we demonstrate that CPP rapidly stimulates histone deacetylase (HDAC) 5 phosphorylation and nuclear export in rat hippocampal neurons. These effects are accompanied by calcium/calmodulin kinase II (CaMKII) and protein kinase D (PKD) phosphorylation. Behavioral experiments revealed that viral-mediated hippocampal knockdown of HDAC5 blocked the antidepressant effects of CPP in stressed animals. Taken together, our results imply that CPP acts via HDAC5 and suggest that HDAC5 is a common regulator contributing to the antidepressant actions of NMDA receptor antagonists such as CPP.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosforilação
/
Fosfotransferases
/
Proteínas Quinases
/
Histonas
/
N-Metilaspartato
/
Modelos Animais
/
Transporte Ativo do Núcleo Celular
/
Depressão
/
Hipocampo
/
Histona Desacetilases
Limite:
Animais
Idioma:
Inglês
Revista:
The Korean Journal of Physiology and Pharmacology
Ano de publicação:
2018
Tipo de documento:
Artigo
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