Treatment with trimethyltin promotes the formation of cleaved tau in the rat brain

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.