Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김용석 | - |
dc.date.accessioned | 2017-09-28T07:12:35Z | - |
dc.date.available | 2017-09-28T07:12:35Z | - |
dc.date.issued | 2015-12 | - |
dc.identifier.citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 112, NO 51, Page. 15755-15760 | en_US |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://www.pnas.org/content/112/51/15755 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11754/29471 | - |
dc.description.abstract | Ketamine produces rapid antidepressant-like effects in animal assays for depression, although the molecular mechanisms underlying these behavioral actions remain incomplete. Here, we demonstrate that ketamine rapidly stimulates histone deacetylase 5 (HDAC5) phosphorylation and nuclear export in rat hippocampal neurons through calcium/calmodulin kinase II-and protein kinase D-dependent pathways. Consequently, ketamine enhanced the transcriptional activity of myocyte enhancer factor 2 (MEF2), which leads to regulation of MEF2 target genes. Transfection of a HDAC5 phosphorylation-defective mutant (Ser259/Ser498 replaced by Ala259/Ala498, HDAC5-S/A), resulted in resistance to ketamine-induced nuclear export, suppression of ketamine-mediated MEF2 transcriptional activity, and decreased expression of MEF2 target genes. Behaviorally, viral-mediated hippocampal knockdown of HDAC5 blocked or occluded the antidepressant effects of ketamine both in unstressed and stressed animals. Taken together, our results reveal a novel role of HDAC5 in the actions of ketamine and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of ketamine. | en_US |
dc.description.sponsorship | This research was supported by the National Research Foundation of Korea Grant 2011-0028317, funded by the Ministry of Education, Science, and Technology, Republic of Korea. | en_US |
dc.language.iso | en | en_US |
dc.publisher | NATL ACAD SCIENCES | en_US |
dc.subject | ketamine | en_US |
dc.subject | HDAC | en_US |
dc.subject | depression | en_US |
dc.subject | hippocampus | en_US |
dc.title | Ketamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats | en_US |
dc.type | Article | en_US |
dc.relation.no | 51 | - |
dc.relation.volume | 112 | - |
dc.identifier.doi | 10.1073/pnas.1513913112 | - |
dc.relation.page | 15755-15760 | - |
dc.relation.journal | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.contributor.googleauthor | Choi, Miyeon | - |
dc.contributor.googleauthor | Lee, Seung Hoon | - |
dc.contributor.googleauthor | Wang, Sung Eun | - |
dc.contributor.googleauthor | Ko, Seung Yeon | - |
dc.contributor.googleauthor | Song, Mihee | - |
dc.contributor.googleauthor | Choi, June-Seek | - |
dc.contributor.googleauthor | Kim, Yong-Seok | - |
dc.contributor.googleauthor | Duman, Ronald S. | - |
dc.contributor.googleauthor | Son, Hyeon | - |
dc.relation.code | 2015002960 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | yongsk | - |
dc.identifier.orcid | http://orcid.org/0000-0001-5062-7408 | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.