title: Type II glucocorticoid receptors are involved in neuronal death and astrocyte activation induced by trimethyltin in the rat hippocampus.
abstract: According 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.
authors.affiliation: Regional Environment Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, 305-0053, Japan. imahide@nies.go.jp
authors.forename: H
authors.initials: H
authors.lastname: Imai
authors.forename: T
authors.initials: T
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Sadamatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Kabuto
authors.forename: N
authors.initials: N
authors.lastname: Kato
mesh_terms: D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology; D005938:Glucocorticoids / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000378:metabolism*; D014298:Trimethyltin Compounds / Q000494:pharmacology*; D014746:Vimentin / Q000096:biosynthesis
chemical_list: D005904:Glial Fibrillary Acidic Protein; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D014298:Trimethyltin Compounds; D014746:Vimentin; C046488:trimethyltin; D000450:Aldosterone; D003907:Dexamethasone