TRIMETHYLTIN SYNDROME AS A HIPPOCAMPAL DEGENERATION MODEL - TEMPORAL CHANGES AND NEUROCHEMICAL FEATURES OF SEIZURE SUSCEPTIBILITY AND LEARNING IMPAIRMENT

The effects of trimethyltin on the hippocampus were investigated in te rms of changes in hislology, depth electroencephalography, learning ac quisition and memory retention, choline acetyltransferase and neuropep tides, and seizure-induced c-fos messenger RNA expression. The results were as follows. (1) Morphologically, trimethyltin produced a progres sive loss of hippocampal CA3 and CA4 pyramidal cells, starting from fo ur days after peroral treatment with trimethyltin hydroxide (9 mg/kg), as described previously. (2) Neurophysiologically the increased seizu re susceptibility to pentylenetetrazol treatment reached a maximum al four days post-trimethyltin and then declined after five days post-tri methyltin. The maximal seizure susceptibility al four days post-trimet hyltin was confirmed by the immediate and long-lasting appearance of s pike discharge in the hippocampus. However, this was not verified by t he expression of c-fos messenger RNA in the hippocampus, which was com parable between trimethyltin-treated and control rats. (3) Behaviorall y, the time-courses of aggression and learning impairment were similar to that of the seizure susceptibility. (4) Neurochemically, trimethyl tin treatment caused changes of neurochemical markers, which were mani fested by the elevation of neuropeptide Y content in the entorhinal co rtex, and of choline acetyltransferase in the hippocampal CA3 subfield . Trimethyltin may offer potential as a fool for investigations on the relationship between neuronal death in the hippocampus and the develo pment of seizure susceptibility and learning impairment. Alterations i n glucocorticoids, glutamate and neuropeptides may all contribute to t he manifestation of the trimethyltin syndrome. (C) 1997 IBRO. Publishe d by Elsevier Science Ltd.