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タイトル :Contribution of endogenous glycine and d-serine to excitotoxic and ischemic cell death in rat cerebrocortical slice cultures
著者 :Katsuki, Hiroshi
Watanabe, Yoshinori
Fujimoto, Shinji
Kume, Toshiaki
Akaike, Akinori
刊行年月日 :2007-8-9
収録雑誌名 :Life Sciences
巻 :81
号 :9
開始ページ :740
終了ページ :749
要約(Abstract) :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.
URL :http://www.elsevier.com/wps/find/journaldescription.cws_home/525477/description#description
収録種別 :雑誌掲載論文
ISSN :00243205
出版社(者) :Elsevier Inc.
権利(Rights) :© 2007 Published by Elsevier Inc.
備考 :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
URI :http://hdl.handle.net/2298/10014
関連 :http://hdl.handle.net/2298/9868
このアイテムの引用には次の識別子を使用してください: http://hdl.handle.net/2298/10014