Hwang In Koo, Yoo Ki-Yeon, Nam Young Sam, Choi Jung Hoon, Lee In Se, Kwon Young-Guen, Kang Tae-Cheon, Kim Yong-Sun, Won Moo Ho
Department of Anatomy, College of Medicine, Hallym University, Chunchon, South Korea.
Neurosci Res. 2006 Apr;54(4):319-27. doi: 10.1016/j.neures.2005.12.012. Epub 2006 Feb 13.
In the present study, we observed expression and changes of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the gerbil hippocampal CA1 region, but not in the CA2/3 region, after 5 min of transient forebrain ischemia. In blood, corticosterone levels were increased biphasically at 30 min and 12 h after ischemia/reperfusion, and thereafter its levels were decreased. In the sham-operated group, MR and GR immunoreactivities were weakly detected in the CA1 region. By 3 days after ischemia, MR and GR were not significantly altered in the CA1 region: at 12 h after ischemia, GR was expressed in a few neurons in the CA1 region, whereas MR was not expressed in any neurons after ischemic insult. From 4 days after ischemia, MR and GR immunoreactivities were detected in astrocytes and microglia in the CA1 region, and at 7 days after ischemia, MR and GR immunoreactivities peaked in the hippocampal CA1 region. At this time, 55% of astrocytes and 30% of microglia showed MR immunoreactivity, and 20% of astrocytes and 40% of microglia showed GR immunoreactivity. Western blot analyses showed that the pattern of changes in MR and GR protein levels was similar to the immunohistochemical changes observed after transient forebrain ischemia. From 4 days after ischemia, MR and GR protein levels were increased time-dependently after ischemia. In conclusion, enhanced MR and GR expressions in astrocytes and microglia were detected in the hippocampal CA1 region 4-7 days after ischemia/reperfusion. At this time, GR immunoreactivity was abundant in microglia, whereas MR immunoreactivity was prominent in astrocytes. The specific distribution of corticosteroid receptors in the astrocytes and microglia may be associated with the differences of MR and GR functions against ischemic damage.
在本研究中，我们观察了沙土鼠短暂性前脑缺血5分钟后，海马CA1区而非CA2/3区盐皮质激素受体（MR）和糖皮质激素受体（GR）的表达及变化。在血液中，缺血/再灌注后30分钟和12小时皮质酮水平呈双相升高，此后其水平下降。在假手术组中，CA1区仅微弱检测到MR和GR免疫反应性。缺血后3天，CA1区的MR和GR无明显改变：缺血后12小时，CA1区少数神经元表达GR，而缺血损伤后任何神经元均未表达MR。缺血后4天起，在CA1区的星形胶质细胞和小胶质细胞中检测到MR和GR免疫反应性，缺血后7天，海马CA1区MR和GR免疫反应性达到峰值。此时，55%的星形胶质细胞和30%的小胶质细胞显示MR免疫反应性，20%的星形胶质细胞和40%的小胶质细胞显示GR免疫反应性。蛋白质印迹分析表明，MR和GR蛋白水平的变化模式与短暂性前脑缺血后观察到的免疫组化变化相似。缺血后4天起，缺血后MR和GR蛋白水平呈时间依赖性升高。总之，缺血/再灌注后4 - 7天，在海马CA1区检测到星形胶质细胞和小胶质细胞中MR和GR表达增强。此时，小胶质细胞中GR免疫反应性丰富，而星形胶质细胞中MR免疫反应性突出。皮质类固醇受体在星形胶质细胞和小胶质细胞中的特异性分布可能与MR和GR对缺血损伤的功能差异有关。
