Type II glucocorticoid receptors are involved in neuronal death and astrocyte activation induced by trimethyltin in the rat hippocampus

According to our previous study, trimethyltin (TMT), a neurotoxicant, induc es 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-adrenocortica l axis is related to neuronal loss in the hippocampus, we evaluated the eff ects of bilateral adrenalectomy (ADX) and the chronic supplemental treatmen t of glucocorticoid receptor agonists after ADX on TMT-induced hippocampal damage. Peroral administration of a single dose of TMT (9 mg/kg body wt) in duced the extensive loss of CA3 pyramidal neurons and reactive astrocytosis in the hippocampus, as evidenced by results of vimentin and glial fibrilla ry acidic protein immunohistochemistry, and the effects were profoundly exa cerbated by bilateral adrenalectomy. Prolonged administration of corticoste rone 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 corticostero ne, suggesting a novel neuroprotective action of type II glucocorticoid rec eptors in the hippocampus. (C) 2001 Academic Press.