CRMP2 mediates GSK3 beta actions in the striatum on regulating neuronal structure and mania-like behavior
DC Field | Value | Language |
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dc.contributor.author | Kim, Wonju | - |
dc.contributor.author | Won, Seong-Yeon | - |
dc.contributor.author | Yoon, Bong-June | - |
dc.date.accessioned | 2021-09-01T19:05:06Z | - |
dc.date.available | 2021-09-01T19:05:06Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2019-02-15 | - |
dc.identifier.issn | 0165-0327 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/67635 | - |
dc.description.abstract | Background: Genetic and physiological studies have implicated the striatum in bipolar disorder (BD). Although Glycogen synthase kinase 3 beta (GSK3 beta) has been suggested to play a role in the pathophysiology of BD since it is inhibited by lithium, it remains unknown how GSK3 beta activity might be involved. Therefore we examined the functional roles of GSK3 beta and one of its substrates, CRMP2, within the striatum. Methods: Using CRISPR-Cas9 system, we specifically ablated GSK3 beta in the striatal neurons in vivo and in vitro. Sholl analysis was performed for the structural studies of medium spiny neurons (MSNs) and amphetamine-induced hyperlocomotion was measured to investigate the effects of gene ablations on the mania-like symptom of BD. Results: GSK3 beta deficiency in cultured neurons and in neurons of adult mouse brain caused opposite patterns of neurite changes. Furthermore, specific knockout of GSK3 beta in the MSNs of the indirect pathway significantly suppressed amphetamine-induced hyperlocomotion. We demonstrated that these phenotypes of GSK3 beta ablation were mediated by CRMP2, a major substrate of GSK3 beta. Limitations: Amphetamine-induced hyperlocomotion only partially recapitulate the symptoms of BD. It requires further study to examine whether abnormality in GSK3 beta or CRMP2 is also involved in depression phase of BD. Additionally, we could not confirm whether the behavioral changes observed in GSK3 beta-ablated mice were indeed caused by the cellular structural changes observed in the striatal neurons. Conclusion: Our results demonstrate that GSK3 beta and its substrate CRMP2 critically regulate the neurite structure of MSNs and their functions specifically within the indirect pathway of the basal ganglia network play a critical role in manifesting mania-like behavior of BD. Moreover, our data also suggest lithium may exert its effect on BD through a GSK3 beta-independent mechanism, in addition to the GSK3 beta inhibition-mediated mechanism. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.subject | GLYCOGEN-SYNTHASE KINASE-3-BETA | - |
dc.subject | BIPOLAR DISORDER | - |
dc.subject | BASAL GANGLIA | - |
dc.subject | DORSAL STRIATUM | - |
dc.subject | GENE | - |
dc.subject | SCHIZOPHRENIA | - |
dc.subject | REWARD | - |
dc.subject | LITHIUM | - |
dc.subject | PROTEIN-2 | - |
dc.subject | DYSREGULATION | - |
dc.title | CRMP2 mediates GSK3 beta actions in the striatum on regulating neuronal structure and mania-like behavior | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Yoon, Bong-June | - |
dc.identifier.doi | 10.1016/j.jad.2018.10.371 | - |
dc.identifier.scopusid | 2-s2.0-85057570610 | - |
dc.identifier.wosid | 000456697100132 | - |
dc.identifier.bibliographicCitation | JOURNAL OF AFFECTIVE DISORDERS, v.245, pp.1079 - 1088 | - |
dc.relation.isPartOf | JOURNAL OF AFFECTIVE DISORDERS | - |
dc.citation.title | JOURNAL OF AFFECTIVE DISORDERS | - |
dc.citation.volume | 245 | - |
dc.citation.startPage | 1079 | - |
dc.citation.endPage | 1088 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | ssci | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Neurosciences & Neurology | - |
dc.relation.journalResearchArea | Psychiatry | - |
dc.relation.journalWebOfScienceCategory | Clinical Neurology | - |
dc.relation.journalWebOfScienceCategory | Psychiatry | - |
dc.subject.keywordPlus | GLYCOGEN-SYNTHASE KINASE-3-BETA | - |
dc.subject.keywordPlus | BIPOLAR DISORDER | - |
dc.subject.keywordPlus | BASAL GANGLIA | - |
dc.subject.keywordPlus | DORSAL STRIATUM | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | SCHIZOPHRENIA | - |
dc.subject.keywordPlus | REWARD | - |
dc.subject.keywordPlus | LITHIUM | - |
dc.subject.keywordPlus | PROTEIN-2 | - |
dc.subject.keywordPlus | DYSREGULATION | - |
dc.subject.keywordAuthor | Bipolar disorder | - |
dc.subject.keywordAuthor | Striatum | - |
dc.subject.keywordAuthor | Medium spiny neuron | - |
dc.subject.keywordAuthor | GSK3 beta | - |
dc.subject.keywordAuthor | CRMP2 | - |
dc.subject.keywordAuthor | Dendritic spine | - |
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