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.
Exp Neurol. 2001 Sep;171(1):22-8. doi: 10.1006/exnr.2001.7725.
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.
根据我们之前的研究，神经毒素三甲基锡（TMT）会导致大鼠海马体中的锥体神经元丧失，在此之前血浆皮质酮浓度会短暂升高。为了探究下丘脑-垂体-肾上腺皮质轴的这种短暂激活是否与海马体中的神经元丧失有关，我们评估了双侧肾上腺切除术（ADX）以及ADX后长期补充糖皮质激素受体激动剂对TMT诱导的海马体损伤的影响。口服单剂量的TMT（9毫克/千克体重）会导致海马体中CA3锥体神经元大量丧失以及反应性星形细胞增生，波形蛋白和胶质纤维酸性蛋白免疫组织化学结果证明了这一点，并且双侧肾上腺切除术会使这些影响显著加剧。长期给予皮质酮不仅减弱了肾上腺切除术的加剧作用，还部分逆转了TMT诱导的神经元丧失和反应性星形细胞增生。地塞米松而非醛固酮可以替代皮质酮，这表明II型糖皮质激素受体在海马体中具有一种新的神经保护作用。
