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Contribution of endogenous glycine and d-serine to excitotoxic and ischemic cell death in rat cerebrocortical slice cultures
http://hdl.handle.net/2298/10014
http://hdl.handle.net/2298/10014edf58c96-b4a4-4c5b-94b2-e21f7294e1e7
名前 / ファイル | ライセンス | アクション |
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Life Sci0081-0740.pdf (323.9 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2008-12-02 | |||||
タイトル | ||||||
タイトル | Contribution of endogenous glycine and d-serine to excitotoxic and ischemic cell death in rat cerebrocortical slice cultures | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題 | Cortical neurons, Glutamate, Excitotoxicity, Ischemia | |||||
資源タイプ | ||||||
資源タイプ | journal article | |||||
著者 |
香月, 博志
× 香月, 博志× 渡辺, 佳典× 藤本, 真二× 久米, 利明× 赤池, 昭紀 |
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別言語の著者 |
香月, 博志
× 香月, 博志× 渡辺, 佳典× 藤本, 真二× 久米, 利明× 赤池, 昭紀 |
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内容記述 | ||||||
内容記述 | N-methyl-d-aspartate (NMDA) receptors, whose activation requires glycine site stimulation, play crucial roles in various physiological and pathological conditions in the brain. We investigated the regulatory roles of potential endogenous glycine site agonists, glycine and d-serine, in excitotoxic and ischemic cell death in the cerebral cortex. Cytotoxicity of NMDA on rat cerebrocortical slice cultures was potentiated by addition of glycine or d-serine. In contrast, cell death induced by oxygen/glucose deprivation (OGD) was not affected by exogenous glycine or d-serine, although blockade of NMDA receptors by MK-801 abolished cell death. In addition, higher concentrations of 2,7-dichlorokynurenic acid (DCKA), a competitive glycine site antagonist, were required to suppress OGD-induced cell death than those to suppress NMDA cytotoxicity. We also found that OGD triggered a robust increase in extracellular glycine. A glycine transporter blocker ALX 5407 increased the extracellular level of glycine, and the protective effect of DCKA against NMDA cytotoxicity was diminished in the presence of ALX 5407. Sensitivity of NMDA cytotoxicity to DCKA was also diminished by l-serine that increased the extracellular level of d-serine. These results indicate that both glycine and d-serine can act as endogenous ligands for NMDA receptor glycine site in the cerebral cortex, and that endogenous glycine may saturate the glycine site under ischemic conditions. The present findings are important for the interpretation of the mechanisms of NMDA and OGD cytotoxicity. | |||||
書誌情報 |
Life Sciences 巻 81, 号 9, p. 740-749, 発行年 2007-08-09 |
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ISSN | ||||||
収録物識別子 | 00243205 | |||||
書誌レコードID | ||||||
収録物識別子 | AA00717011 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
関連識別子 | 10.1016/j.lfs.2007.07.001 | |||||
権利 | ||||||
権利情報 | © 2007 Published by Elsevier Inc. | |||||
フォーマット | ||||||
内容記述 | application/pdf | |||||
形態 | ||||||
323884 bytes | ||||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
日本十進分類法 | ||||||
主題 | 491.17 | |||||
出版者 | ||||||
出版者 | Elsevier Inc. | |||||
資源タイプ | ||||||
内容記述 | 論文(Article) | |||||
資源タイプ・ローカル | ||||||
雑誌掲載論文 | ||||||
資源タイプ・NII | ||||||
Journal Article | ||||||
資源タイプ・DCMI | ||||||
text | ||||||
資源タイプ・ローカル表示コード | ||||||
01 | ||||||
部分である | ||||||
関連タイプ | isPartOf | |||||
関連識別子 | http://hdl.handle.net/2298/9868 | |||||
URL | ||||||
内容記述 | http://www.elsevier.com/wps/find/journaldescription.cws_home/525477/description#description | |||||
コメント | ||||||
平成18~19年度科学研究費補助金(基盤研究(C))研究成果報告書 課題番号:18590052『ミクログリアの活性化を介する黒質線条体系ニューロン変性の機序とその防御』pp.133-142に掲載 |