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http://dx.doi.org/10.4196/kjpp.2018.22.2.155

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

Park, Min Hyeop (Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering)
Choi, Miyeon (Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University)
Kim, Yong-Seok (Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering)
Son, Hyeon (Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.22, no.2, 2018 , pp. 155-162 More about this Journal
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.
Keywords
Depression; Hippocampus; Histone deacetylase 5; NMDA receptor antagonist; Phosphorylation;
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