{"created":"2021-03-01T06:40:30.269546+00:00","id":34053,"links":{},"metadata":{"_buckets":{"deposit":"ce62815c-ef74-483c-9c4a-f7c7014546e6"},"_deposit":{"id":"34053","owners":[],"pid":{"revision_id":0,"type":"depid","value":"34053"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:00034053","sets":["453:456","471:537:538:2006"]},"item_7_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"The Effect of Neuronal Excitement on APP processing in Cultured Cells"}]},"item_7_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019-04","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"4","bibliographicPageEnd":"184","bibliographicPageStart":"173","bibliographicVolumeNumber":"133","bibliographic_titles":[{"bibliographic_title":"新潟医学会雑誌"}]}]},"item_7_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"アルツハイマー病(Alzheimer's disease: AD)の主要な病理変化の一つは神経細胞外に沈着するβ-アミロイド(β-amyloid: Aβ)から構成される老人斑である．Aβはアミロイド前駆体タンパク(amyloid precursor protein: APP)からβ-secretaseおよびγ-secretaseにより産生される．近年，脳機能画像研究からAD早期における神経活動の充進と病態進展の関係性が示唆されている．本研究では興奮性神経伝達物質であるグルタミン酸による持続的な神経細胞興奮がAβ産生を含むAPP processingに及ぼす影響について検証した．神経細胞興奮の程度と興奮の持続時間に依存したAPP processingの変化を捉えるため，ラット大脳皮質由来初代神経培養細胞(胎生17日)を用いた刺激実験系で検討した．グルタミン酸の添加濃度及び時間を段階的に設定し薬剤添加後に細胞溶解液及び培養上清を回収し，発現タンパクについてウエスタンブロット法あるいはsandwich ELISA法による解析を行った神経細胞興奮はearly growth response factor-1(EGR-1)の発現により評価した．グルタミン酸(0.1-100µM)添加によりEGR-1の一過性の発現増加をみとめ，高濃度であるほどEGR-1の発現はより増加し持続時間も延長した．グルタミン酸100µMでは添加2時間で全長型APPの発現が一過性に低下し，これに伴いAPP C末端断片β(APP-CTFβ)も発現が抑制された．一方，グルタミン酸0.1µMでは添加2時間でAPP-CTFβの発現亢進，添加24時間で可溶性APPβ (soluble APPβ,sAPPβ)の発現充進およびAβ増加がみられた．これらの結果から，高濃度のグルタミン酸による神経細胞興奮はAβ産生に抑制的に，一方，低濃度のグルタミン酸による持続的な神経細胞興奮はAβ産生に促進的に働くと考えられた．本研究は，持続的な神経細胞の興奮がAβ産生亢進を介しAD病態に関与することを示唆し，持続する神経興奮の抑制がADの新たな治療ターゲットとなる可能性を支持する．","subitem_description_type":"Abstract"}]},"item_7_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"175138","nameIdentifierScheme":"WEKO"}],"names":[{"name":"Ishiguro, Takanobu"}]}]},"item_7_publisher_7":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"新潟医学会"}]},"item_7_select_19":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_select_item":"publisher"}]},"item_7_source_id_11":{"attribute_name":"書誌レコードID","attribute_value_mlt":[{"subitem_source_identifier":"AN00182415","subitem_source_identifier_type":"NCID"}]},"item_7_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"00290440","subitem_source_identifier_type":"ISSN"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"石黒, 敬信"}],"nameIdentifiers":[{"nameIdentifier":"60848","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-09-14"}],"displaytype":"detail","filename":"133(4)_173-184.pdf","filesize":[{"value":"6.3 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"133(4)_173-184","url":"https://niigata-u.repo.nii.ac.jp/record/34053/files/133(4)_173-184.pdf"},"version_id":"55c72c37-85c1-4790-9929-513fa64e8606"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"アルツハイマー病","subitem_subject_scheme":"Other"},{"subitem_subject":"神経細胞興奮","subitem_subject_scheme":"Other"},{"subitem_subject":"アミロイド前駆体タンパク","subitem_subject_scheme":"Other"},{"subitem_subject":"β-アミロイド","subitem_subject_scheme":"Other"},{"subitem_subject":"APP processing","subitem_subject_scheme":"Other"},{"subitem_subject":"グルタミン酸","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"神経細胞興奮がamyloid precursor protein (APP)のprocessingへ及ぼす影響","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"神経細胞興奮がamyloid precursor protein (APP)のprocessingへ及ぼす影響"}]},"item_type_id":"7","owner":"1","path":["456","2006"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-09-14"},"publish_date":"2020-09-14","publish_status":"0","recid":"34053","relation_version_is_last":true,"title":["神経細胞興奮がamyloid precursor protein (APP)のprocessingへ及ぼす影響"],"weko_creator_id":"1","weko_shared_id":2},"updated":"2022-12-15T04:04:21.970453+00:00"}