Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow 226001, U.P., India.
Neuroscience. 2013 Jan 29;230:172-83. doi: 10.1016/j.neuroscience.2012.10.034. Epub 2012 Oct 22.
The present study was conducted to correlate rotenone-induced neurotoxicity with cellular and molecular modifications in neuronal and neuronal supportive cells in rat brain regions. Rotenone was administered (3, 6 and 12 μg/μl) intranigrally in adult male Sprague-Dawley rats. After the 7th day of rotenone treatment, specific protein markers for neuronal cells - tyrosine hydroxylase (TH), astroglial cells - glial fibrillary acidic protein (GFAP), microglial cells - CD11b/c, and Iba-1 were evaluated by immunoblotting and immunofluorescence in the striatum (STR) and mid brain (MB). Apoptotic cell death was assessed by caspase-3 gene expression. Higher doses of rotenone significantly lowered TH protein levels and elevated Iba-1 levels in MB. All the doses of rotenone significantly increased GFAP and CD11b/c protein in the MB. In STR, rotenone elevated GFAP levels but did not affect TH, CD11b/c and Iba-1 protein levels. Caspase-3 expression was increased significantly by all the doses of rotenone in MB but in STR only by higher doses (6 and 12 μg). It may be suggested that astroglial activation and apoptosis play an important role in rotenone-induced neurotoxicity. MB appeared as more sensitive than STR toward rotenone-induced cell toxicity. The astroglial cells emerged as more susceptible than neuronal and microglial cells to rotenone in STR.
本研究旨在探讨鱼藤酮诱导的神经毒性与大鼠脑区神经元和神经元支持细胞的细胞和分子变化之间的相关性。鱼藤酮（3、6 和 12 μg/μl）被颅内给予成年雄性 Sprague-Dawley 大鼠。在鱼藤酮处理的第 7 天，通过免疫印迹和免疫荧光法评估纹状体（STR）和中脑（MB）中神经元细胞的特异性蛋白标志物 - 酪氨酸羟化酶（TH）、星形胶质细胞 - 胶质纤维酸性蛋白（GFAP）、小胶质细胞 - CD11b/c 和 Iba-1。通过 caspase-3 基因表达评估细胞凋亡。较高剂量的鱼藤酮显著降低了 MB 中的 TH 蛋白水平，并升高了 Iba-1 水平。鱼藤酮的所有剂量均显著增加了 MB 中的 GFAP 和 CD11b/c 蛋白。在 STR 中，鱼藤酮升高了 GFAP 水平，但不影响 TH、CD11b/c 和 Iba-1 蛋白水平。所有剂量的鱼藤酮均显著增加了 MB 中的 caspase-3 表达，但在 STR 中仅在较高剂量（6 和 12 μg）时增加。这表明星形胶质细胞的激活和凋亡在鱼藤酮诱导的神经毒性中起重要作用。MB 对鱼藤酮诱导的细胞毒性比 STR 更为敏感。星形胶质细胞比神经元和小胶质细胞更容易受到 STR 中鱼藤酮的影响。
