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- Title
The antidepressant action of 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid is mediated by phosphorylation of histone deacetylase 5.
- Authors
Min Hyeop Park; Miyeon Choi; Yong-Seok Kim; Hyeon Son
- 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.
- Subjects
ANTIDEPRESSANTS; PHOSPHONIC acids; METHYL aspartate antagonists; HIPPOCAMPUS (Brain); HISTONE deacetylase inhibitors; THERAPEUTICS
- Publication
Korean Journal of Physiology & Pharmacology, 2018, Vol 22, Issue 2, p155
- ISSN
1226-4512
- Publication type
Article
- DOI
10.4196/kjpp.2018.22.2.155