{"created":"2023-05-15T14:59:25.579515+00:00","id":80628,"links":{},"metadata":{"_buckets":{"deposit":"5b8acace-49d3-498c-a632-4a9f5b69533c"},"_deposit":{"created_by":1,"id":"80628","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"80628"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00080628","sets":["1"]},"author_link":["1010865","1010861","1010862","1010864","1010860","1010857","1010858","1010863","1010859","1010855","1010856"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-09","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"2","bibliographicPageEnd":"563","bibliographicPageStart":"550","bibliographicVolumeNumber":"58","bibliographic_titles":[{"bibliographic_title":"Molecular Neurobiology"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Pharmacological studies have implicated the translocator protein (TSPO) in the regulation of complex behaviors including\nanxiety and depression, effects thought to be mediated by increased synthesis of neuroactive steroid hormones. However,\nTSPO function in the brain remains to be corroborated in vivo via genetic studies. To address this, we developed global TSPO\nknockout (TSPO-KO) and neuronal TSPO transgenic (TSPO-Tg) mouse models to investigate TSPO function in the regulation\nof anxiety- and depression-related behaviors using elevated plus maze and forced swim test paradigms. Neuroactive steroid\nhormones were measured in the brain by mass spectrometry. In vivo TSPO ligand pharmacokinetics was investigated using\ncompetitive PET with 18F-FE-DAA1106. Genetic TSPO deficiency increased anxiety-related behavior and impaired brain\nsteroidogenesis but did not affect depressive behaviors. Using the TSPO-KO model, we then demonstrated the specificity of\nAc-5216, also known as XBD-173 or Emapunil, as an anxiolytic targeting TSPO at doses optimized by competitive PET for high\ncortical occupancy. Neuronal TSPO overexpression decreased depressive behaviors, an effect that was dependent on steroidogenesis,\nand partially reversed anxiogenic behavior in TSPO-KOmice. These findings demonstrate that TSPO is critical for brain\nsteroidogenesis and modulates anxiety- and depression-related behaviors. However, we demonstrate that key differences in the\ncontribution of neuronal TSPO to the modulation of these complex behaviors, illustrating the tissue- and cell-specific importance\nof TSPO. The TSPO-KO and TSPO-Tg mice provide the tools and rationale for the development of therapeutic approaches\ntargeting TSPO in the brain for treatment of neuropsychiatric conditions.","subitem_description_type":"Abstract"}]},"item_8_relation_13":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"32989676","subitem_relation_type_select":"PMID"}}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1007/s12035-020-02136-5","subitem_relation_type_select":"DOI"}}]},"item_8_relation_17":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://link.springer.com/article/10.1007/s12035-020-02136-5","subitem_relation_type_select":"URI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0893-7648","subitem_source_identifier_type":"ISSN"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Barron, Anna"}],"nameIdentifiers":[{"nameIdentifier":"1010855","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Higuchi, Makoto"}],"nameIdentifiers":[{"nameIdentifier":"1010856","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hattori, Satoko"}],"nameIdentifiers":[{"nameIdentifier":"1010857","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kito, Seiji"}],"nameIdentifiers":[{"nameIdentifier":"1010858","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Suhara, Tetsuya"}],"nameIdentifiers":[{"nameIdentifier":"1010859","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ji, Bin"}],"nameIdentifiers":[{"nameIdentifier":"1010860","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Barron, Anna","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1010861","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Makoto, Higuchi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1010862","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Satoko, Hattori","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1010863","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tetsuya, Suhara","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1010864","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ji, Bin","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1010865","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Regulation of Anxiety and Depression by Mitochondrial Translocator Protein-Mediated Steroidogenesis: the Role of Neurons ","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Regulation of Anxiety and Depression by Mitochondrial Translocator Protein-Mediated Steroidogenesis: the Role of Neurons "}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-10-02"},"publish_date":"2020-10-02","publish_status":"0","recid":"80628","relation_version_is_last":true,"title":["Regulation of Anxiety and Depression by Mitochondrial Translocator Protein-Mediated Steroidogenesis: the Role of Neurons "],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T19:02:16.290076+00:00"}