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Nitric oxide-producing microglia mediate thrombin-induced degeneration of dopaminergic neurons in rat midbrain slice culture
http://hdl.handle.net/2298/10009
http://hdl.handle.net/2298/10009ef81aede-c213-4590-8b0e-d9a909bd1eda
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
J Neu0097-1232.pdf (1.2 MB)
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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 | Nitric oxide-producing microglia mediate thrombin-induced degeneration of dopaminergic neurons in rat midbrain slice culture | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題 | Dopamine neuron, Inflammation, Mitogen-activated protein kinase, Neurodegeneration, Parkinson's disease | |||||
| 資源タイプ | ||||||
| 資源タイプ | journal article | |||||
| 著者 |
香月, 博志
× 香月, 博志× Okawara, Mitsugu× Shibata, Haruki× 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× 大川原, 賦× 柴田, 治樹× 久米, 利明× 赤池, 昭紀 |
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| 内容記述 | ||||||
| 内容記述 | Activated microglia are considered to play important roles in degenerative processes of midbrain dopaminergic neurons. Here we examined mechanisms of neurotoxicity of thrombin, a protease known to trigger microglial activation, in organotypic midbrain slice cultures. Thrombin induced a progressive decline in the number of dopaminergic neurons, an increase in nitric oxide (NO) production, and whole tissue injury indicated by lactate dehydrogenase release and propidium iodide uptake. Microglia expressed inducible NO synthase (iNOS) in response to thrombin, and inhibition of iNOS rescued dopaminergic neurons without affecting whole tissue injury. Inhibitors of mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK) attenuated thrombin-induced iNOS induction and dopaminergic cell death. Whole tissue injury was also attenuated by inhibition of ERK and p38 MAPK. Moreover, depletion of resident microglia from midbrain slices abrogated thrombin-induced NO production and dopaminergic cell death, but did not inhibit tissue injury. Finally, antioxidative drugs prevented thrombin-induced dopaminergic cell death without affecting whole tissue injury. Hence, NO production resulting from MAPK-dependent microglial iNOS induction is a crucial event in thrombin-induced dopaminergic neurodegeneration, whereas damage of other midbrain cells is MAPK-dependent but is NO-independent. | |||||
| 書誌情報 |
Journal of Neurochemistry 巻 97, 号 5, p. 1232-1242, 発行年 2006-06 |
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| ISSN | ||||||
| 収録物識別子 | 00223042 | |||||
| 書誌レコードID | ||||||
| 収録物識別子タイプ | NCID | |||||
| 収録物識別子 | AA00703243 | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 関連識別子 | 10.1111/j.1471-4159.2006.03752.x | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| 形態 | ||||||
| 1210829 bytes | ||||||
| 著者版フラグ | ||||||
| 出版タイプ | AM | |||||
| 日本十進分類法 | ||||||
| 主題Scheme | NDC | |||||
| 主題 | 491.17 | |||||
| 出版者 | ||||||
| 出版者 | Blackwell Science | |||||
| 資源タイプ | ||||||
| 内容記述タイプ | Other | |||||
| 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 | |||||
| 識別子タイプ | URI | |||||
| 関連識別子 | http://hdl.handle.net/2298/9868 | |||||
| URL | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | http://www.blackwellpublishing.com/jnc_enhanced/ | |||||
| 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.33-43に掲載 | ||||||
