The type 1 interleukin 1 receptor is not required for the death of murine hippocampal dentate granule cells and microglia activation
The type 1 interleukin 1 receptor is not required for the death of murine hippocampal dentate granule cells and microglia activation
复制标题
DOI：
10.1016/j.brainres.2007.11.076
复制
发表时间：
2008-02-15
期刊：
影响因子：
2.9
通讯作者：
Aoyama, Mineyoshi
中科院分区：
文献类型：
--
作者：
Harry, G. Jean;Funk, Jason A.;Aoyama, Mineyoshi
在白细胞介素-1 (IL-1) 的操纵以及通过 1 型 IL-1 受体 (IL-1R1) 的后续信号传导下，观察到炎症过程、神经元死亡和神经胶质细胞反应的变化。为了研究 IL-1R1 激活对化学诱导的小鼠海马损伤病理生理学的影响，我们检查了暴露于氢氧化三甲基锡（2.0 mg TMT/kg，腹膜内）的雄性断奶小鼠的神经元死亡和神经炎症的水平和模式。通过活性 caspase 3 免疫染色和凝集素阳性小胶质细胞的存在检测到，齿状颗粒细胞死亡发生在 TMT 后 6 小时。随着 TNF α 和 IL-1 α mRNA 水平的升高，神经元死亡和小胶质细胞反应的严重程度增加了 12-24 小时。在 IL-1R1 null (IL-1R1(-/-)) 小鼠中，TMT 后 24 或 72 小时神经元死亡的模式和严重程度与野生型 (WT) 小鼠相似。在两组中，TNF α 和 MIP-1 α 的 mRNA 水平均升高，IL-1 α 或 IL-β 未见显着变化，并且小胶质细胞的早期激活（包括其进展为吞噬表型的能力）得以维持。与WT小鼠相比，IL-1R1(-/-)小鼠表现出有限的胶质纤维酸性蛋白(GFAP)星形细胞反应，以及优先诱导Fas信号成分的mRNA水平。总的来说，这些结果表明 IL-1R1 激活对于 TMT 诱导的齿状颗粒神经元死亡或小胶质细胞局部激活不是必需的；然而，IL-1R1 信号传导参与介导星形胶质细胞对损伤的结构反应，并可能通过 Fas 信号传导成分调节细胞凋亡机制。由 Elsevier B.V. 出版
Alterations in inflammatory process, neuronal death, and glia response have been observed under manipulation of interleukin-1 (IL-1) and subsequent signaling through the type 1 IL-1 receptor (IL-1R1). To investigate the influence of IL-1R1 activation in the pathophysiology of a chemical-induced injury to the murine hippocampus, we examined the level and pattern of neuronal death and neuroinflammation in male weanling mice exposed to trimethyltin hydroxide (2.0 mg TMT/kg, i.p.). Dentate granule cell death occurred at 6 h post-TMT as detected by active caspase 3 immunostaining and presence of lectin positive microglia. The severity of neuronal death and microglia response increased by 12-24 h with elevations in mRNA levels for TNF alpha and IL-1 alpha. In IL-1R1 null (IL-1R1(-/-)) mice, the pattern and severity of neuronal death at 24 or 72 h post-TMT was similar as compared to wildtype (WT) mice. In both groups, mRNA levels for TNF alpha and MIP-1 alpha were elevated, no significant change was seen in either IL-1 alpha or IL-beta, and the early activation of microglia, including their ability to progress to a phagocytic phenotype, was maintained. Compared to WT mice, IL-1R1(-/-) mice displayed a limited glial fibrillary acidic protein (GFAP) astrocytic response, as well as a preferential induction in mRNA levels of Fas signaling components. Cumulatively, these results indicate that IL-1R1 activation is not necessary for TMT-induced death of dentate granule neurons or local activation of microglia; however, IL-1R1 signaling is involved in mediating the structural response of astrocytes to injury and may regulate apoptotic mechanisms via Fas signaling components. Published by Elsevier B.V.