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Ketamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats

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dc.contributor.authorChoi, Miyeon-
dc.contributor.authorLee, Seung Hoon-
dc.contributor.authorWang, Sung Eun-
dc.contributor.authorKo, Seung Yeon-
dc.contributor.authorSong, Mihee-
dc.contributor.authorChoi, June-Seek-
dc.contributor.authorKim, Yong-Seok-
dc.contributor.authorDuman, Ronald S.-
dc.contributor.authorSon, Hyeon-
dc.date.accessioned2022-07-15T20:03:44Z-
dc.date.available2022-07-15T20:03:44Z-
dc.date.created2021-05-12-
dc.date.issued2015-12-
dc.identifier.issn0027-8424-
dc.identifier.urihttps://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/155766-
dc.description.abstractKetamine 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.-
dc.language영어-
dc.language.isoen-
dc.publisherNATL ACAD SCIENCES-
dc.titleKetamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats-
dc.typeArticle-
dc.contributor.affiliatedAuthorKim, Yong-Seok-
dc.contributor.affiliatedAuthorSon, Hyeon-
dc.identifier.doi10.1073/pnas.1513913112-
dc.identifier.scopusid2-s2.0-84952701116-
dc.identifier.wosid000366916000064-
dc.identifier.bibliographicCitationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.112, no.51, pp.15755 - 15760-
dc.relation.isPartOfPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-
dc.citation.titlePROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-
dc.citation.volume112-
dc.citation.number51-
dc.citation.startPage15755-
dc.citation.endPage15760-
dc.type.rimsART-
dc.type.docTypeArticle-
dc.description.journalClass1-
dc.description.isOpenAccessN-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.relation.journalResearchAreaScience & Technology - Other Topics-
dc.relation.journalWebOfScienceCategoryMultidisciplinary Sciences-
dc.subject.keywordPlusMESSENGER-RNA TRANSLATION-
dc.subject.keywordPlusNMDA RECEPTOR BLOCKADE-
dc.subject.keywordPlusHIPPOCAMPAL-NEURONS-
dc.subject.keywordPlusDEPRESSION-
dc.subject.keywordPlusTRANSCRIPTION-
dc.subject.keywordPlusEXPRESSION-
dc.subject.keywordPlusFACTOR-2-
dc.subject.keywordPlusPROTEIN-
dc.subject.keywordPlusCAMP-
dc.subject.keywordPlusACTIVATION-
dc.subject.keywordAuthorketamine-
dc.subject.keywordAuthorHDAC-
dc.subject.keywordAuthordepression-
dc.subject.keywordAuthorhippocampus-
dc.identifier.urlhttps://www.pnas.org/content/112/51/15755-
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