Possible pathogenic mechanisms on trimethyltin-induced lesions in the hippocampus of adult and neonatal rats

Abstract

The extent of trimethyltin (TMT) induced lesions in the rat hippocampal formation was reviewed. Adult rats were treated with a single dose of 6.0 mg TMT/kg body wt and were sacrificed between 3-60 d following exposure. In the hippocampal formation, the granule cells of fascia dentata showed early changes, which subsided considerably at a later time of the intoxication. On the other hand, destruction of the pyramidal neurons in the Ammon's horn became more pronounced with time, resulting in an extensive destruction of this structure. It is interesting to note that the CA3 neurons in the septal portion of the Ammon's horn were more vulnerable than those located more temporally, whereas the reverse pattern was observed for the dentate granule cells as well as for the CA1,2 neurons of the Ammon's horn. Special stain for zinc (Timm's method) also revealed a progressive depletion of zinc in the mossy fibers. When neonatal rats were treated at various times with a single injection of TMT, rapid and progressive destruction of the Ammon's horn was observed in animals injected between postnatal day (PND) 5-15. The progression of neuronal involvement was CA3b →CA3a, b →CA3(a,b,c)→CA3+CA2→entire Ammon's horn (CA1,2,3). This pattern of pathological lesion was in good concert with morphological development and functional maturity of the hippocampal formation. Destruction of the Ammon's horn neurons was proposed to be the result of hyperexcitation of the dentate granule neurons under the influence of TMT. Other possible mechanisms are also discussed.