TRIMETHYLTIN

1: Exp Neurol. 2001 Sep;171(1):22-8.
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Type II glucocorticoid receptors are involved in neuronal death and astrocyte activation induced by trimethyltin in the rat hippocampus.Imai H, Nishimura T, Sadamatsu M, Liu Y, Kabuto M, Kato N.Regional Environment Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, 305-0053, Japan. imahide@nies.go.jpAccording to our previous study, trimethyltin (TMT), a neurotoxicant, induces the loss of pyramidal neurons in the rat hippocampus, which is preceded by a transient increase in plasma corticosterone concentration. To address whether this transient activation of the hypothalamopituitary-adrenocortical axis is related to neuronal loss in the hippocampus, we evaluated the effects of bilateral adrenalectomy (ADX) and the chronic supplemental treatment of glucocorticoid receptor agonists after ADX on TMT-induced hippocampal damage. Peroral administration of a single dose of TMT (9 mg/kg body wt) induced the extensive loss of CA3 pyramidal neurons and reactive astrocytosis in the hippocampus, as evidenced by results of vimentin and glial fibrillary acidic protein immunohistochemistry, and the effects were profoundly exacerbated by bilateral adrenalectomy. Prolonged administration of corticosterone not only attenuated the exacerbating effects of adrenalectomy but also partially reversed the TMT-induced neuronal loss and reactive astrocytosis. Dexamethasone, but not aldosterone, could be substituted for corticosterone, suggesting a novel neuroprotective action of type II glucocorticoid receptors in the hippocampus.
2: Brain Res. 1988 Sep 20;460(2):346-51.
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Parallel changes in operant behavioral adaptation and hippocampal corticosterone binding in rats treated with trimethyltin.Gerbec EN, Messing RB, Sparber SB.Department of Pharmacology, University of Minnesota Medical School, Minneapolis 55455.Rats were given water vehicle or trimethyltin (TMT; 3.0, 6.0 or 7.5 mg/kg, p.o.). ...........Corticosterone binding to hippocampal cytosolic protein was maximally reduced for the group given 6.0 mg TMT/kg. The greatest reduction in hippocampal weight resulted from injection of 7.5 mg TMT/kg, but a smaller reduction in [3H]corticosterone binding (i.e. 22%) was observed for this group. In the absence of an effect of 3.0 mg TMT/kg upon weight of hippocampus, there also was a reduction in steroid binding, indicating the sensitivity of this parameter for TMT toxicity. The results support the notion that hippocampal corticosteroid receptors are important for behavioral adaptation, and rats given moderate doses of TMT may be useful for studying functions of corticosterone receptors.Publication Types:

3: Neurosci Res. 2005 Mar;51(3):319-27.
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Neurosci Res. 2004 Oct;50(2):209-17. Cytokines participate in neuronal death induced by trimethyltin in the rat hippocampus via type II glucocorticoid receptors.Liu Y, Imai H, Sadamatsu M, Tsunashima K, Kato N.Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. liuying-tky@umin.ac.jpWe investigated the role of IL-1alpha and IL-1beta expressed in the reactive gliosis following hippocampal damage induced by trimethyltin (TMT). IL-1alpha immunoreactivity was expressed earlier in small glial cells on day 4 post-TMT, while IL-1beta expression was obvious in large swollen glial cells on day 14 post-TMT. Both IL-1alpha and IL-1beta immunoreactivities were double-labeled with astrocyte marker, vimentin, but not with a microglia marker, OX-42. The expression of both IL-1alpha/beta was enhanced by adrenalectomy (ADX) prior to TMT administration. Corticosterone (CORT) or dexamethasone (DEX) supplementation not only cancelled effects of ADX, but also partially reversed TMT-induced enhancement of IL-1alpha/beta expressions. These changes coincided with TMT-induced neuronal death in CA3 pyramidal cells of the hippocampus. It is suggested that IL-1alpha/beta expressed in reactive astrocytes participate in TMT neurotoxicity via type II glucocorticoid receptors.