3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid 의 histone deacetylase 5 인산화에 의한 항우울효과에 대한 연구

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. Here, I showed that CPP rapidly stimulates histone deacetylase (HDAC) 5 phosphorylation and nuclear export in rat hippocampal neurons. Consequently, BDNF protein levels increased rapidly with the administration of CPP. Behavioral experiments revealed that CPP induced an antidepressant-like response and substantiated that viral-mediated hippocampal knockdown of HDAC5 blocked the antidepressant effects of CPP in stressed animals. Taken together, these results imply that CPP acts via HDAC5.