The antidepressant action of 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid is mediated by phosphorylation of histone deacetylase 5.
10.4196/kjpp.2018.22.2.155
- Author:
Min Hyeop PARK
1
;
Miyeon CHOI
;
Yong Seok KIM
;
Hyeon SON
Author Information
1. Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering, Seoul 04763, Korea. hyeonson@hanyang.ac.kr, yongsk@hanyang.ac.kr
- Publication Type:Original Article
- Keywords:
Depression;
Hippocampus;
Histone deacetylase 5;
NMDA receptor antagonist;
Phosphorylation
- MeSH:
Active Transport, Cell Nucleus;
Animals;
Depression;
Hippocampus;
Histone Deacetylases*;
Histones*;
Models, Animal;
N-Methylaspartate;
Neurons;
Phosphorylation*;
Phosphotransferases;
Protein Kinases;
Rats
- From:The Korean Journal of Physiology and Pharmacology
2018;22(2):155-162
- CountryRepublic of Korea
- Language:English
-
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.
