Trimethyltin-Induced Hippocampal Neurodegeneration is Possibly Mediated by Induction of Apoptosis

ABSTRACT

BACKGROUND: Trimethyltin (TMT) is a neurotoxicant which produces a distinct pattern of neuronal cell death in the hippocampus following systemic administration of a single dose. However, the mechanism of selective neuronal death remains unclear. We performed this study to elucidate the underlying mechanism of TMT-induced hippocampal neu-ronal death. METHODS: The effects of trimethyltin (8.0mg/kg, I.p., single dose) on the hippocampal neurons were investi-gated in terms of changes in the neurobehavioral status, histologic, and electron microscopc findings. RESULTS: Behaviorally, TMT treatment caused stereotypic limbic system dysfunction, i.e. tremors, spontaneous seizures, vocaliza-tion, hyperactivity, hyperexcitability, intraspecific aggression as described previously. Morphologically, TMT produced prominent neurodegeneration in the dentate gyrus. Widespread, strong glial fibrillary acidic protein (GFAP) immunore-activity, which was suggestive of reactive astrogliosis, was noted throughout the hippocampal subfields. Many degener-ating neurons were TUNEL positive. Electron microscopic findings revealed characteristic features of apoptosis in the dentate granule cells. NADPH-diaphorase positive cells were spared after TMT exposure. CONCLUSIONS: It is suggested that TMT-induced hippocampal degeneration might be a useful in vivo model for the study of learning and memory, neuronal-glial interactions, and selective neuronal apoptosis.