Council of Scientific and Industrial Research, Indian Institute of Toxicology Research-Council of Scientific and Industrial Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow-226001, Uttar Pradesh, India.
Toxicol Sci. 2011 Aug;122(2):526-38. doi: 10.1093/toxsci/kfr115. Epub 2011 May 10.
The study aimed to identify the differentially expressed nigrostriatal proteins in cypermethrin-induced neurodegeneration and to investigate the role of microglial activation therein. Proteomic approaches were used to identify the differentially expressed proteins. Microglial activation, tyrosine hydroxylase immunoreactivity (TH-IR), dopamine content, and neurobehavioral changes were measured according to the standard procedures. The expressions of α-internexin intermediate filament (α-IIF), ATP synthase D chain (ATP-SD), heat shock protein (Hsp)-70, truncated connexin-47, Hsp-60, mitogen-activated protein kinase-activated kinase-5, nicotinamide adenine dinucleotide dehydrogenase 24k chain precursor, platelet-activating factor acetyl hydrolase 1b-α2 (PAF-AH 1b-α2), and synaptosomal-associated protein-25 (SNAP-25) were altered in the substantia nigra and nicotinamide adenine dinucleotide- specific isocitrate dehydrogenase, phosphatidylethanolamine-binding protein-1, prohibitin, protein disulfide isomerase-endoplasmic reticulum 60 protease, stathmin, and ubiquitin-conjugating enzyme in the striatum along with motor impairment, decreased dopamine and TH-IR, and increased microglial activation after cypermethrin exposure. Minocycline restored α-IIF, ATP-SD chain, truncated connexin-47, Hsp-60, PAF-AH 1b-α2, stathmin and SNAP-25 expressions, motor impairment, dopamine, TH-IR, and microglial activation. The results suggest that cypermethrin produces microglial activation-dependent and -independent changes in the expression patterns of the nigrostriatal proteins leading to dopaminergic neurodegeneration.
本研究旨在鉴定氯菊酯诱导的神经退行性变中黑质纹状体差异表达蛋白，并探讨小胶质细胞活化在此过程中的作用。采用蛋白质组学方法鉴定差异表达蛋白。根据标准程序测量小胶质细胞活化、酪氨酸羟化酶免疫反应性（TH-IR）、多巴胺含量和神经行为变化。α-中间丝蛋白（α-IIF）、三磷酸腺苷合酶 D 链（ATP-SD）、热休克蛋白（Hsp）-70、截短型连接蛋白-47、Hsp-60、丝裂原活化蛋白激酶激活的激酶-5、烟酰胺腺嘌呤二核苷酸脱氢酶 24k 链前体、血小板激活因子乙酰水解酶 1b-α2（PAF-AH 1b-α2）和突触相关蛋白-25（SNAP-25）在黑质和烟酰胺腺嘌呤二核苷酸特异性异柠檬酸脱氢酶、磷酯酰乙醇胺结合蛋白-1、抑制素、蛋白二硫键异构酶内质网 60 蛋白酶、微管蛋白、泛素结合酶在纹状体中的表达发生改变，同时运动障碍、多巴胺和 TH-IR 减少，以及氯菊酯暴露后小胶质细胞活化增加。米诺环素恢复了α-IIF、ATP-SD 链、截短型连接蛋白-47、Hsp-60、PAF-AH 1b-α2、微管蛋白和 SNAP-25 的表达、运动障碍、多巴胺、TH-IR 和小胶质细胞活化。结果表明，氯菊酯在黑质纹状体蛋白表达模式中产生小胶质细胞活化依赖性和非依赖性变化，导致多巴胺能神经退行性变。
