TRPM2, a Susceptibility Gene for Bipolar Disorder, Regulates Glycogen Synthase Kinase-3 Activity in the Brain
DC Field | Value | Language |
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dc.contributor.author | Jang, Yongwoo | - |
dc.contributor.author | Lee, Sung Hoon | - |
dc.contributor.author | Lee, Byeongjun | - |
dc.contributor.author | Jung, Seungmoon | - |
dc.contributor.author | Khalid, Arshi | - |
dc.contributor.author | Uchida, Kunitoshi | - |
dc.contributor.author | Tominaga, Makoto | - |
dc.contributor.author | Jeon, Daejong | - |
dc.contributor.author | Oh, Uhtaek | - |
dc.date.accessioned | 2022-07-15T21:27:51Z | - |
dc.date.available | 2022-07-15T21:27:51Z | - |
dc.date.created | 2021-05-13 | - |
dc.date.issued | 2015-08 | - |
dc.identifier.issn | 0270-6474 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/156557 | - |
dc.description.abstract | Bipolar disorder (BD) is a psychiatric disease that causes mood swings between manic and depressed states. Although genetic linkage studies have shown an association between BD and TRPM2, a Ca2+-permeable cation channel, the nature of this association is unknown. Here, we show that D543E, a mutation of Trpm2 that is frequently found in BD patients, induces loss of function. Trpm2-deficient mice exhibited BD-related behavior such as increased anxiety and decreased social responses, along with disrupted EEG functional connectivity. Moreover, the administration of amphetamine in wild-type mice evoked a notable increase in open-field activity that was reversed by the administration of lithium. However, the anti-manic action of lithium was not observed in the Trpm2(-/-) mice. The brains of Trpm2(-/-) mice showed a marked increase in phosphorylated glycogen synthase kinase-3 (GSK-3), a key element in BD-like behavior and a target of lithium. In contrast, activation of TRPM2 induced the dephosphorylation of GSK-3 via calcineurin, a Ca2+-dependent phosphatase. Importantly, the overexpression of the D543E mutant failed to induce the dephosphorylation of GSK-3. Therefore, we conclude that the genetic dysfunction of Trpm2 causes uncontrolled phosphorylation of GSK-3, which may lead to the pathology of BD. Our findings explain the long-sought etiologic mechanism underlying the genetic link between Trpm2 mutation and BD. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | Society for Neuroscience | - |
dc.title | TRPM2, a Susceptibility Gene for Bipolar Disorder, Regulates Glycogen Synthase Kinase-3 Activity in the Brain | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Jang, Yongwoo | - |
dc.identifier.doi | 10.1523/JNEUROSCI.5251-14.2015 | - |
dc.identifier.scopusid | 2-s2.0-84940398568 | - |
dc.identifier.wosid | 000362501900006 | - |
dc.identifier.bibliographicCitation | Journal of Neuroscience, v.35, no.34, pp.11811 - 11823 | - |
dc.relation.isPartOf | Journal of Neuroscience | - |
dc.citation.title | Journal of Neuroscience | - |
dc.citation.volume | 35 | - |
dc.citation.number | 34 | - |
dc.citation.startPage | 11811 | - |
dc.citation.endPage | 11823 | - |
dc.type.rims | ART | - |
dc.type.docType | 정기학술지(Article(Perspective Article포함)) | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Neurosciences & Neurology | - |
dc.relation.journalWebOfScienceCategory | Neurosciences | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | MOUSE MODEL | - |
dc.subject.keywordPlus | PREFRONTAL CORTEX | - |
dc.subject.keywordPlus | MANIC SYMPTOMS | - |
dc.subject.keywordPlus | FRONTAL-CORTEX | - |
dc.subject.keywordPlus | LITHIUM | - |
dc.subject.keywordPlus | BEHAVIOR | - |
dc.subject.keywordPlus | SCHIZOPHRENIA | - |
dc.subject.keywordPlus | ABNORMALITIES | - |
dc.subject.keywordPlus | CONNECTIVITY | - |
dc.subject.keywordAuthor | bipolar disorder | - |
dc.subject.keywordAuthor | calcineurin | - |
dc.subject.keywordAuthor | glycogen synthase kinase-3 | - |
dc.subject.keywordAuthor | mutation | - |
dc.subject.keywordAuthor | susceptibilty | - |
dc.subject.keywordAuthor | TRPM2 | - |
dc.identifier.url | https://www.jneurosci.org/content/35/34/11811 | - |
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