{"created":"2023-07-25T10:25:34.021340+00:00","id":5963,"links":{},"metadata":{"_buckets":{"deposit":"81af1eb9-74a8-41ba-bd71-bdb27642ab54"},"_deposit":{"created_by":3,"id":"5963","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"5963"},"status":"published"},"_oai":{"id":"oai:air.repo.nii.ac.jp:00005963","sets":["611:939:940"]},"author_link":["17791","17793","17792","17789","17790"],"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2018","bibliographicIssueDateType":"Issued"},"bibliographicVolumeNumber":"8","bibliographic_titles":[{"bibliographic_title":"SCIENTIFIC REPORTS"}]}]},"item_10001_description_5":{"attribute_name":"内容記述（抄録）","attribute_value_mlt":[{"subitem_description":"In a rat ex vivo acute glaucoma model, high pressure (75 mmHg) causes swelling of ganglion cell axons and elevates levels of the endogenous steroids 24(S)-hydroxycholesterol (24SH) and allopregnanolone (AlloP). Furthermore, 24SH (0.1 mu M) alone elevates AlloP levels via NMDA receptors. With this model, we now investigate possible interactions between 24SH and AlloP. We found that inhibition of AlloP synthesis with dutasteride under high pressure results in severe excitotoxicity in addition to axonal swelling. The excitotoxicity is prevented by exogenous AlloP but not 24SH, indicating that endogenous AlloP is crucial for protection. However, inhibition of 24SH synthesis with voriconazole induces severe excitotoxicity under normal pressure. Paradoxically, the excitotoxicity by voriconazole is better prevented by AlloP than 24SH. These findings suggest that inhibition of 24SH synthesis becomes excitotoxic in the absence of AlloP. We also observed that co-administration of sub-micromolar 24SH (0.1 mu M) and AlloP (0.1 mu M), concentrations that are only partially effective when administered alone, prevents axonal swelling under high pressure. This apparent enhanced protection indicates strong interaction between the two neurosteroids to preserve neuronal integrity, with 24SH contributing to AlloP synthesis via NMDA receptors and with AlloP playing an essential role in neuroprotection via GABA(A) receptors.","subitem_description_type":"Other"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Nature Research"}]},"item_10001_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1038/s41598-018-31239-2","subitem_relation_type_select":"DOI"}}]},"item_10001_relation_25":{"attribute_name":"関連リンク","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"http://dx.doi.org/10.1038/s41598-018-31239-2"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://dx.doi.org/10.1038/s41598-018-31239-2","subitem_relation_type_select":"DOI"}}]},"item_10001_rights_15":{"attribute_name":"著作権等","attribute_value_mlt":[{"subitem_rights":"Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2018"}]},"item_10001_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"2045-2322","subitem_source_identifier_type":"ISSN"}]},"item_10001_version_type_20":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Ishikawa, Makoto"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yoshitomi, Takeshi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Covey, DouglasF."}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Zorumski, CharlesF."}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Izumi, Yukitoshi"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2023-02-25"}],"displaytype":"detail","filename":"iA_2022_101.pdf","filesize":[{"value":"6.7 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"iA_2022_101.pdf","url":"https://air.repo.nii.ac.jp/record/5963/files/iA_2022_101.pdf"},"version_id":"3b9b08d8-86c8-4ec4-82aa-b8343b820e1a"}]},"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":"Additive neuroprotective effects of 24(S)-hydroxycholesterol and allopregnanolone in an ex vivo rat glaucoma model","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Additive neuroprotective effects of 24(S)-hydroxycholesterol and allopregnanolone in an ex vivo rat glaucoma model"}]},"item_type_id":"10001","owner":"3","path":["940"],"pubdate":{"attribute_name":"公開日","attribute_value":"2023-02-25"},"publish_date":"2023-02-25","publish_status":"0","recid":"5963","relation_version_is_last":true,"title":["Additive neuroprotective effects of 24(S)-hydroxycholesterol and allopregnanolone in an ex vivo rat glaucoma model"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2023-07-25T10:39:07.197034+00:00"}