Quantitative Assessment of Trimethyltin Induced Pathology of the Hippocampus

Abstract

The pathology induced by trimethyltin in the hippocampus was investigated using a detailed morphometric model. Male Long-Evans rats were dosed with 3 mg/kg trimethyltin chloride (TMT) for three consecutive days and sacrificed at subsequent interim periods. Total brain volume was not significantly affected; hippocampus volume decreased within 4 days after completion of dose. Pyramidal cells were more sensitive to the toxic effects of TMT than granule cells, in addition, dorsal pyramidal cells appeared to be more sensitive than ventral pyramidal cells. The dorsal CA4 region appeared to be the most susceptible to cell loss, although the dorsal CA1 region also exhibited significant reductions. The most dramatic reduction in cell numbers occurred between 14 and 28 days post-dose. Cell loss within the CA3c and CA4 but not the CA1 region was preceded by decreased nuclear volume. In addition cellular loss within the dorsal CA1 region appeared to be most pronounced within a well defined rectangular patch of cells immediately adjacent to the CA3-CA1 junction. The data further suggest that TMT is a potent toxicant to the hippocampus. This toxicity is delayed, and selectively affects well defined groups of cells within the structure. Additionally, differences in nuclear pathology suggest that more than one mechanism may be involved in the destruction of these target cell populations.