A morphometric analysis of trimethyltin-induced change in rat brain using the Timm technique

Rats were given a single gavage of trimethyltin chloride (TMT) providing a dose of 0, 4.3, or 6.7 mg/kg of alkyltin. Gross changes in brain structures were quantified and analyzed statistically. Behavioral and functional measures were taken to verify efficacy of TMT dose. The high dose produced transient weight loss and seizures. In the fourth week after gavage, the high dose produced hyperactivity in the residential maze and activity wheel. High and low TMT doses decreased auditory startle responsiveness. Estrus cycle was normal in all groups. Brains were sectioned and stained with the Timm stain which delimited subregions of hippocampus and connected structures and also revealed mossy fibers. Linear and areal measures were made at three positions along the septotemporal axis of Ammon's horn. The low dose produced reductions in size in a few isolated subareas of the brain. The high dose produced, at the three planes studied, extensive (15-40%) loss of tissue in Ammon's horn and structures to which Ammon's horn is interconnected--subiculum, entorhinal cortex, dentate gyrus, hilus, CA3, and CA1 region. Neocortex and caudate-putamen were unaffected. These findings suggest that a single TMT gavage may disrupt brain structures important to linking neocortex with subcortex via structures in the hippocampal region.