Arimoto Toyoko, Bing Guoying
Department of Anatomy and Neurobiology, Medical Center, University of Kentucky, 800 Rose Street, Room MN 225, Lexington, KY 40536-5276, USA.
Neurobiol Dis. 2003 Feb;12(1):35-45. doi: 10.1016/s0969-9961(02)00017-7.
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.
本研究旨在探讨诱导型一氧化氮合酶（iNOS）的表达是否参与脂多糖（LPS）诱导的大鼠黑质（SN）神经退行性变，并研究一氧化氮（NO）在SN多巴胺能神经元丢失中的作用。在蛋白质免疫印迹分析中，注射LPS后，SN中iNOS呈时间和剂量依赖性诱导表达。免疫荧光和免疫组织化学分析显示，iNOS定位于具有特征性阿米巴样形态的完全活化的小胶质细胞中。此外，给予L-N(G)-硝基精氨酸（一种一氧化氮合酶的选择性抑制剂）和糖皮质激素地塞米松可显著抑制LPS诱导的多巴胺能神经元丢失。这些iNOS抑制剂可降低LPS诱导的小胶质细胞活化，提示NO在炎症介导的小胶质细胞活化中起作用。这些结果表明，LPS诱导SN中活化小胶质细胞表达iNOS，并且NO和/或其代谢产物可能在炎症介导的多巴胺能神经元变性中起关键作用。
