Department of Anatomy with Radiology and The Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Mol Neurodegener. 2009 Dec 31;4:55. doi: 10.1186/1750-1326-4-55.
Exposure to toxins/chemicals is considered to be a significant risk factor in the pathogenesis of Parkinson's disease (PD); one putative chemical is the naturally occurring herbicide rotenone that is now used widely in establishing PD models. We, and others, have shown that chronic low dose rotenone treatment induces excessive accumulation of Reactive Oxygen Species (ROS), inclusion body formation and apoptosis in dopaminergic neurons of animal and human origin. Some studies have also suggested that microglia enhance the rotenone induced neurotoxicity. While the effects of rotenone on neurons are well established, there is little or no information available on the effect of rotenone on microglial cells, and especially cells of human origin. The aim of the present study was to investigate the effects of chronic low dose rotenone treatment on human microglial CHME-5 cells.
We have shown previously that rotenone induced inclusion body formation in human dopaminergic SH-SY5Y cells and therefore used these cells as a control for inclusion body formation in this study. SH-SY5Y and CHME-5 cells were treated with 5 nM rotenone for four weeks. At the end of week 4, both cell types were analysed for the presence of inclusion bodies, superoxide dismutases and cell activation (only in CHME-5 cells) using Haematoxylin and Eosin staining, immunocytochemical and western blotting methods. Levels of active caspases and ROS (both extra and intra cellular) were measured using biochemical methods.
The results suggest that chronic low dose rotenone treatment activates human microglia (cell line) in a manner similar to microglia of animal origin as shown by others. However human microglia release excessive amounts of ROS extracellularly, do not show excessive amounts of intracellular ROS and active caspases and most importantly do not show any protein aggregation or inclusion body formation. Human microglia appear to be resistant to rotenone (chronic, low dose) induced damage.
接触毒素/化学物质被认为是帕金森病（PD）发病机制的一个重要危险因素；一种假定的化学物质是天然存在的除草剂鱼藤酮，它现在被广泛用于建立 PD 模型。我们和其他人已经表明，慢性低剂量鱼藤酮处理会导致动物和人类来源的多巴胺能神经元中活性氧（ROS）过度积累、包涵体形成和细胞凋亡。一些研究还表明，小胶质细胞增强了鱼藤酮诱导的神经毒性。虽然鱼藤酮对神经元的影响已经得到很好的证实，但关于鱼藤酮对小胶质细胞的影响，特别是对人类来源的小胶质细胞的影响，几乎没有或没有信息。本研究旨在探讨慢性低剂量鱼藤酮处理对人小胶质细胞 CHME-5 的影响。
我们之前已经表明，鱼藤酮诱导人多巴胺能 SH-SY5Y 细胞中包涵体的形成，因此在本研究中使用这些细胞作为包涵体形成的对照。用 5 nM 鱼藤酮处理 SH-SY5Y 和 CHME-5 细胞 4 周。在第 4 周末，使用苏木精和伊红染色、免疫细胞化学和 Western 印迹方法分析两种细胞类型中包涵体、超氧化物歧化酶和细胞激活（仅在 CHME-5 细胞中）的存在。使用生化方法测量活性半胱天冬酶和 ROS（细胞内外）的水平。
结果表明，慢性低剂量鱼藤酮处理以类似于其他研究中显示的动物来源的小胶质细胞的方式激活人小胶质细胞（细胞系）。然而，人小胶质细胞细胞外释放过多的 ROS，细胞内不显示过多的 ROS 和活性半胱天冬酶，最重要的是不显示任何蛋白质聚集或包涵体形成。人小胶质细胞似乎对鱼藤酮（慢性、低剂量）诱导的损伤具有抗性。
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