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Paraquat induces long-lasting dopamine overflow through the excitotoxic pathway in the striatum of freely moving rats

https://asahikawa-med.repo.nii.ac.jp/records/139
https://asahikawa-med.repo.nii.ac.jp/records/139
b341146a-fb80-4d3e-9465-e08e8b573afd
名前 / ファイル ライセンス アクション
218.pdf 218.pdf (430.9 kB)
Item type 学術雑誌論文 / Journal Article_02(1)
公開日 2007-02-14
タイトル
タイトル Paraquat induces long-lasting dopamine overflow through the excitotoxic pathway in the striatum of freely moving rats
言語 en
言語
言語 eng
資源タイプ
資源タイプ journal article
著者 清水, 恵子

× 清水, 恵子

清水, 恵子

ja-Kana シミズ, ケイコ

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Matsubara, K

× Matsubara, K

Matsubara, K

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Ohtaki, K

× Ohtaki, K

Ohtaki, K

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Fujimaru, S

× Fujimaru, S

Fujimaru, S

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Saito, O

× Saito, O

Saito, O

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Shiono, H

× Shiono, H

Shiono, H

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著者 ローマ字
Shimizu, Keiko
出版社 ローマ字
ELSEVIER SCIENCE BV
書誌情報 BRAIN RESEARCH

巻 976, 号 2, p. 243-252, 発行日 2003-06-01
ISSN
収録物識別子タイプ ISSN
収録物識別子 0006-8993
DOI
関連タイプ isVersionOf
識別子タイプ DOI
関連識別子 10.1016/S0006-8993(03)02750-1
リンクURL
内容記述タイプ Other
内容記述 http://www.sciencedirect.com/science/journal/00068993 | http://www.sciencedirect.com/science/journal/00068993
抄録
内容記述タイプ Abstract
内容記述 The herbicide paraquat is an environmental factor that could be involved in the etiology of Parkinson’s disease. We have previously shown that paraquat penetrates through the blood–brain barrier and is taken up by neural cells. In this study, we examined the in vivo toxic mechanism of paraquat to dopamine neurons. GBR-12909, a selective dopamine transporter inhibitor, reduced paraquat uptake into the striatal tissue including dopaminergic terminals. The subchronic treatment with systemic paraquat significantly decreased brain dopamine content in the striatum and slightly in the midbrain and cortex, and was accompanied by the diminished level of its acidic metabolites in rats. When paraquat was administered through a microdialysis probe, a transitory increase in the extracellular levels of glutamate, followed by long-lasting elevations of the extracellular levels of Nox− (NO_2− plus NO_3−) and dopamine were detected in the striatum of freely moving rats. This dopamine overflow lasted for more than 24 h after the paraquat treatment. Dopamine overflow was inhibited by N^G-nitro-_L-arginine methyl ester, dizocilpine, 6,7-dinitroquinoxaline-2,3-dione and _L-deprenyl. The toxic mechanism of paraquat involves glutamate induced activation of non-NMDA receptors, resulting in activation of NMDA receptor-channels. The influx of Ca^2+ into cells stimulates nitric oxide synthase. Released NO would diffuse to dopaminergic terminals and further induce mitochondrial dysfunction by the formation of peroxynitrite, resulting in continuous and long-lasting dopamine overflow. The constant exposure to low levels of paraquat may lead to the vulnerability of dopaminergic terminals in humans, and might potentiate neurodegeneration caused by the exposure of other substances, such as endogenous dopaminergic toxins.
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資源タイプ text
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