The antidepressant action of 3-(2-carboxypiperazin-4-yl)propyl- 1-phosphonic acid is mediated by phosphorylation of histone deacetylase 5

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Min Hyeop Park Miyeon Choi Yong-Seok Kim Hyeon Son
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제22권 제2호, 155~162쪽, 전체 8쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2018.03.31

영문 초록

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.

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INTRODUCTION

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ACKNOWLEDGEMENTS

REFERENCES

키워드

Depression Hippocampus Histone deacetylase 5 NMDA receptor antagonist Phosphorylation