细胞因子通过II型糖皮质激素受体参与三甲基锡诱导的大鼠海马神经元死亡。

Cytokines participate in neuronal death induced by trimethyltin in the rat hippocampus via type II glucocorticoid receptors.

作者信息

Liu Y, Imai H, Sadamatsu M, Tsunashima K, Kato N

机构信息

Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

出版信息

Neurosci Res. 2004 Oct;50(2):209-17. doi: 10.1016/j.neures.2004.06.019.

DOI:10.1016/j.neures.2004.06.019

PMID:15380328

Abstract

We 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.

摘要

我们研究了三甲基锡（TMT）诱导海马损伤后反应性胶质增生中表达的白细胞介素-1α（IL-1α）和白细胞介素-1β（IL-1β）的作用。TMT处理后第4天，IL-1α免疫反应性在小胶质细胞中较早表达，而TMT处理后第14天，IL-1β表达在大的肿胀胶质细胞中明显。IL-1α和IL-1β免疫反应性均与星形胶质细胞标志物波形蛋白双标记，但不与小胶质细胞标志物OX-42双标记。在给予TMT之前进行肾上腺切除术（ADX）可增强IL-1α/β的表达。补充皮质酮（CORT）或地塞米松（DEX）不仅消除了ADX的作用，还部分逆转了TMT诱导的IL-1α/β表达增强。这些变化与TMT诱导的海马CA3锥体细胞神经元死亡一致。提示反应性星形胶质细胞中表达的IL-1α/β通过II型糖皮质激素受体参与TMT神经毒性作用。