{"created":"2023-05-15T14:52:27.165929+00:00","id":71615,"links":{},"metadata":{"_buckets":{"deposit":"fcc25f05-bd55-40d8-8594-b841996345b4"},"_deposit":{"created_by":1,"id":"71615","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"71615"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00071615","sets":["10:28"]},"author_link":["704445","704446","704438","704436","704443","704442","704444","704439","704440","704441","704437"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2013-11-11","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Translocator protein (TSPO) is a multi-functional mitochondrial transmembrane\nprotein primarily localised in steroid-producing tissues, including the brain. TSPO ligands elicit\npleiotropic neuroprotective and cognitive benefits mechanistically linked to the regulation of\nsteroid synthesis and consequently represent emerging treatment strategies for several\nneurodegenerative conditions. To investigate the potential of TSPO as a therapeutic target for\nAlzheimer's disease (AD), the current study assessed the effects of the TSPO ligand Ro5-4864\non the development of neuropathology in the triple transgenic mouse model (3xTgAD). In\n3xTgAD mice, the effects of the TSPO ligand on neurosteroidogenesis and AD-related\nneuropathology including β-amyloid accumulation, gliosis and behavioral impairment were\nexamined under both early intervention (7 month-old young-adult male mice with low\npathology) and treatment (24 month-old, aged male mice with advanced neuropathology)\nconditions. Ro5-4864 treatment not only effectively attenuated development of neuropathology\nand behavioral impairment in young adult mice, but also reversed these indices in aged 3xTgAD\nmice. In the young-adult mice, these benefits were associated with increased brain levels of the\npotent neuroactive steroid hormones, testosterone and progesterone. Because TSPO ligands can\ndifferentially modulate TSPO activities, we also compared the independent and combined effects\nof Ro5-4864 with PK-11195 (a non-benzodiazepine TSPO ligand) on endogenous β-amyloid in\nwild type mice, finding an additive anti-amyloidogenic effect of combined treatment. To\ndetermine the contribution of increased neurosteroid synthesis to the β-amyloid reducing effects\nof Ro5-4864 in the wild type mice, we co-administered Ro5-4864 with a neurosteroidogenesis\ninhibitor, aminoglutethimide. We next compared the effect of old (Ro5-4864, PK-11195) and\nnew-generation TSPO ligands (AC-5216, DAA-1106) on endogenous β-amyloid in wild type\nmice. New generation TSPO ligands such as AC-5216 have already undergone significant\nclinical development for treatment of anxiety disorders and depression, however our findings\nsuggest these ligands may also have a therapeutic potential for the treatment of Alzheimer`s.","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"The Society for Neuroscience meeting 2013","subitem_description_type":"Other"}]},"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":"704436","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"M., GARCIA-SEGURA L."}],"nameIdentifiers":[{"nameIdentifier":"704437","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"CARUSO, D."}],"nameIdentifiers":[{"nameIdentifier":"704438","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"JAYARAMAN, A."}],"nameIdentifiers":[{"nameIdentifier":"704439","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"LEE, J.-W."}],"nameIdentifiers":[{"nameIdentifier":"704440","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"C., MELCANGI R."}],"nameIdentifiers":[{"nameIdentifier":"704441","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ji, Bin"}],"nameIdentifiers":[{"nameIdentifier":"704442","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Higuchi, Makoto"}],"nameIdentifiers":[{"nameIdentifier":"704443","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ｂａｒｒｏｎ Ａｎｎａ","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"704444","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"季 斌","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"704445","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"樋口 真人","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"704446","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":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"Ligand of translocator protein stimulates neurosteroid synthesis and reverses pathology in a mouse model of Alzheimer`s disease","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Ligand of translocator protein stimulates neurosteroid synthesis and reverses pathology in a mouse model of Alzheimer`s disease"}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2015-04-20"},"publish_date":"2015-04-20","publish_status":"0","recid":"71615","relation_version_is_last":true,"title":["Ligand of translocator protein stimulates neurosteroid synthesis and reverses pathology in a mouse model of Alzheimer`s disease"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T19:49:15.713537+00:00"}