Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration
Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration
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DOI：
10.1016/s0969-9961(02)00017-7
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发表时间：
2003-02-01
影响因子：
6.1
通讯作者：
Bing, GY
中科院分区：
文献类型：
--
作者：
Arimoto, T;Bing, GY
本研究旨在探讨诱导型一氧化氮合酶(INOS)的表达是否参与内毒素诱导的大鼠黑质(SN)神经变性，并探讨NO在黑质多巴胺能神经元丢失中的作用。Western印迹分析显示，注射脂多糖后，黑质中iNOS的表达呈时间和剂量依赖性。免疫荧光和免疫组织化学分析显示，iNOS位于完全激活的小胶质细胞中，具有阿米巴样形态特征。此外，一氧化氮合酶选择性抑制剂L-N-G-硝基精氨酸和糖皮质激素地塞米松可显著抑制内毒素诱导的多巴胺能神经元的丢失。这些iNOS抑制剂减少了内毒素诱导的小胶质细胞激活，提示NO在炎症介导的小胶质细胞激活中起作用。这些结果表明，内毒素可诱导黑质内激活的小胶质细胞表达iNOS，NO及其代谢产物可能在炎症介导的多巴胺能神经元变性中起重要作用。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
The present study was designed to examine whether expression of iNOS was involved in LPS-induced neurodegeneration in rat substantia nigra (SN) and to study the role of NO in the loss of the SN dopaminergic neurons. In Western blot analysis, iNOS was induced in the SN after injection of LPS in a time- and dose-dependent manner. Immunofluorescence and immunohistochemical analyses revealed that the iNOS is located in a fully activated microglia with the characteristic amoeboid morphology. Furthermore, LPS-induced loss of dopaminergic neurons was significantly inhibited by the administration of L-N-G-nitroarginine, a selective inhibitor of NOS, and the glucocorticoid dexamethasone. These inhibiting agents for iNOS reduced LPS-induced microglial activation, suggesting that NO has a role in inflammatory-mediated microglial activation. These results demonstrate that LPS induces the expression of iNOS in activated microglia in the SN, and that NO and/or its metabolites may play a crucial role in inflammation-mediated degeneration of dopaminergic neurons. (C) 2003 Elsevier Science (USA). All rights reserved.