title: Trimethyltin syndrome as a hippocampal degeneration model: temporal changes and neurochemical features of seizure susceptibility and learning impairment.
abstract: The effects of trimethyltin on the hippocampus were investigated in terms of changes in histology, depth electroencephalography, learning acquisition and memory retention, choline acetyltransferase and neuropeptides, and seizure-induced c-fos messenger RNA expression. The results were as follows. (1) Morphologically, trimethyltin produced a progressive loss of hippocampal CA3 and CA4 pyramidal cells, starting from four days after peroral treatment with trimethyltin hydroxide (9 mg/kg), as described previously. (2) Neurophysiologically, the increased seizure susceptibility to pentylenetetrazol treatment reached a maximum at four days post-trimethyltin and then declined after five days post-trimethyltin. The maximal seizure susceptibility at four days post-trimethyltin was confirmed by the immediate and long-lasting appearance of spike discharge in the hippocampus. However, this was not verified by the expression of c-fos messenger RNA in the hippocampus, which was comparable between trimethyltin-treated and control rats. (3) Behaviorally, the time-courses of aggression and learning impairment were similar to that of the seizure susceptibility. (4) Neurochemically, trimethyltin treatment caused changes of neurochemical markers, which were manifested by the elevation of neuropeptide Y content in the entorhinal cortex, and of choline acetyltransferase in the hippocampal CA3 subfield. Trimethyltin may offer potential as a tool for investigations on the relationship between neuronal death in the hippocampus and the development of seizure susceptibility and learning impairment. Alterations in glucocorticoids, glutamate and neuropeptides may all contribute to the manifestation of the trimethyltin syndrome.
authors.affiliation: Department of Psychiatry, Shiga University of Medical Science, Otsu, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Ishida
authors.forename: M
authors.initials: M
authors.lastname: Akaike
authors.forename: S
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: H
authors.initials: H
authors.lastname: Kanai
authors.forename: A
authors.initials: A
authors.lastname: Masui
authors.forename: M
authors.initials: M
authors.lastname: Sadamatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: B S
authors.initials: BS
authors.lastname: McEwen
authors.forename: N
authors.initials: N
authors.lastname: Kato
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology*; D009478:Neuropeptide Y / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000473:pathology*; D013004:Somatostatin / Q000378:metabolism; D014298:Trimethyltin Compounds / Q000633:toxicity*
chemical_list: D009478:Neuropeptide Y; D016760:Proto-Oncogene Proteins c-fos; D014298:Trimethyltin Compounds; D013004:Somatostatin; D003346:Corticotropin-Releasing Hormone; D002795:Choline O-Acetyltransferase