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

J Korean Neurol Assoc > Volume 17(6); 1999 > Article

Journal of the Korean Neurological Association 1999;17(6): 861-868.

Trimethyltin으로 유발된 해마 신경세포 사멸의 기전

한설희, 정승연*

충북대학교 의과대학 신경과학교실,성모자애병원 소아과*

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

Seol-Heui Han, M.D., Seung-Yun Chung, M.D.*

Department of Neurology, Chungbuk National University Hospital, Department of Pediatrics, Our Lady of Mercy Hospital*

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. M e t h o d s : 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 electronmicroscopc findings. R e s u l t s : 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. C o n c l u s i o n s : 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. J Korean Neurol Assoc 17(6):861~868, 1999 Key Words : Trimethyltin (TMT), Selective neurodegeneration, Hippocampus, Dentate granule cells, Apoptosis