Straiko M M W, Gudelsky G A, Coolen L M, Harrison R, Zemlan F P
Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio 45267, USA.
J Neurosci Res. 2006 Oct;84(5):1116-23. doi: 10.1002/jnr.21002.
Trimethyltin (TMT) is a well-documented neurotoxin that affects primarily limbic system structures. Most previous studies have relied on histological approaches to examine TMT neurotoxicity, so the aim of this study was to employ the novel biomarker cleaved MAP-tau (C-tau) to assess TMT-induced CNS injury both quantitatively and qualitatively. Immunoblot studies indicated that cleaved MAP-tau proteins with molecular weights of 45-50 kD were present in the hippocampus of rats treated with TMT but not vehicle 21 days after treatment. Quantitative ELISA revealed that C-tau concentration in rats treated with TMT was greatest at 14 and 21 days in the piriform cortex and hippocampus, respectively; TMT did not significantly increase C-tau concentration in the mesencephalon. C-tau immunocytochemistry demonstrated the greatest TMT-induced damage in the hippocampus and piriform cortex. Additional studies utilizing dual immunocytochemistry revealed that C-tau-labeled cells were also glial fibrillary acidic protein-positive, leading to identification of these cells as astrocytes. Although the origin of C-tau in astrocytes of rats treated with TMT is currently unknown, increased C-tau concentration and the presence of C-tau positive cells in limbic system structures of TMT-treated rats further supports the view that C-tau is a reliable marker of CNS toxicity.
三甲基锡（TMT）是一种有充分文献记载的神经毒素，主要影响边缘系统结构。以前的大多数研究都依赖组织学方法来检查TMT的神经毒性，因此本研究的目的是采用新型生物标志物裂解的MAP-τ（C-τ）来定量和定性评估TMT诱导的中枢神经系统损伤。免疫印迹研究表明，分子量为45-50 kD的裂解MAP-τ蛋白存在于TMT处理的大鼠海马中，而在处理21天后给予赋形剂的大鼠海马中则不存在。定量ELISA显示，TMT处理的大鼠梨状皮质和海马中C-τ浓度分别在第14天和第21天最高；TMT并未显著增加中脑的C-τ浓度。C-τ免疫细胞化学显示，TMT诱导的损伤在海马和梨状皮质中最为严重。利用双重免疫细胞化学的进一步研究表明，C-τ标记的细胞也是胶质纤维酸性蛋白阳性，从而确定这些细胞为星形胶质细胞。尽管目前尚不清楚TMT处理的大鼠星形胶质细胞中C-τ的来源，但TMT处理的大鼠边缘系统结构中C-τ浓度的增加和C-τ阳性细胞的存在进一步支持了C-τ是中枢神经系统毒性可靠标志物的观点。
