Cannabinoids prevent lipopolysaccharide-induced neurodegeneration in the rat substantia nigra in vivo through inhibition of microglial activation and NADPH oxidase

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• 作者：Eun Sook Chung^a ; Eugene Bok^a ; ^b ; ¹ ; Young Cheul Chung^a ; ^b ; ² ; Hyung Hwan Baik^a ; ^{hhbaik@khu.ac.kr} ; Byung Kwan Jin^a ; ^b ; ^{bkjin@khu.ac.kr}
• 关键词：Cannabinoids ; LPS ; Microglial activation ; NADPH oxidase ; Oxidative stress ; Proinflammatory cytokines
• 刊名：Brain Research
• 出版年：2012
• 期刊代码：8_00068993
• 类别：neu
• 出版时间：27 April, 2012
• 卷：1451
• 期：Complete
• 页码：110-116
• 文件大小：902 K

摘要

We investigated the effects of synthetic cannabinoids, WIN55,212-2 and HU210, on LPS-injected rat substantia nigra in vivo. Intranigral injection of LPS resulted in a significant loss of nigral dopaminergic (DA) neurons, as determined by Nissl staining and TH immunohistochemistry. LPS-induced neurotoxicity was accompanied by microglial activation, as demonstrated by OX-42 immunohistochemistry. In parallel, Western blot analysis, ELISA assay and hydroethidine histochemistry revealed activation of NADPH oxidase, as demonstrated by increased translocation of the cytosolic proteins p47^phox and p67^phox, generation of reactive oxygen species (ROS) and increased level of proinflammatory cytokines (TNF-伪 and IL-1尾), where degeneration of nigral DA neurons was evident. Interestingly, WIN55,212-2 and HU210 increased the survival of nigral DA neurons at 7 days post-LPS treatment. Consistent with these results, cannabinoids inhibited activation of NADPH oxidase, ROS production and production of proinflammatory cytokines in the rat SN. The present data suggest that cannabinoids may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with microglial activation.