Diverse microglial responses after intrahippocampal administration of lipopolysaccharide
Diverse microglial responses after intrahippocampal administration of lipopolysaccharide
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DOI：
10.1002/glia.20272
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发表时间：
2006-03-01
期刊：
影响因子：
6.2
通讯作者：
Gordon, MN
中科院分区：
文献类型：
--
作者：
Herber, DL;Maloney, JL;Gordon, MN
炎症通过促进神经病理学和临床症状的发展而在阿尔茨海默病的发病机制中起主要作用。然而，这些影响的机制仍然不清楚。脂多糖（LPS）激活先天性免疫反应，并在注射到中枢神经系统时引发神经胶质增生。在本研究中，我们评估了海马内单次注射LPS后小胶质细胞增生的时间进程。小鼠双侧注射4 μ g LPS。注射后存活时间为1、6和24小时，以及3、7、14和28天。对炎症标志物进行蛋白质和RNA分析。24 h后，观察到簇分化标记物CD 45、胶质细胞酸性蛋白（GFAP）、清道夫受体A（SRA）和Fc γ受体mRNA的显著升高。免疫组化显示了一个复杂的模式，小胶质细胞的蛋白质表达，以及细胞形态的变化。Fc γ受体和SRA的RNA和蛋白质一过性升高，在3天达到峰值，1周后恢复至基础水平。相比之下，小胶质细胞在28天时间点保持显著活化，如通过CD 45和补体受体3水平所确定的。这些发现表明对LPS的多变量反应，并且小胶质细胞表型的评价可能导致更好地理解神经炎性疾病。(c)2005 Wiley-Liss，Inc.
Inflammation has been argued to play a primary role in the pathogenesis of Alzheimer's disease by contributing to the development of neuropathology and clinical symptoms. However, the mechanisms underlying these effects remain obscure. Lipopolysaccharide (LPS) activates the innate immune response and triggers gliosis when injected into the central nervous system. In the studies described in the present work, we evaluated the time course of microgliosis after a single intrahippocampal injection of LPS. Mice were injected bilaterally with 4 mu g of LPS. Post-injection survival times were 1, 6, and 24 h, as well as 3, 7, 14, and 28 days. Protein and RNA analyses were performed for inflammatory markers. Significant elevations of cluster differentiation marker CD45, glial fibrillary acidic protein (GFAP), scavenger receptor A (SRA), and Fc gamma receptor mRNA were seen after 24 h. Immunohistochemistry revealed a complex pattern of protein expression by microglia, as well as changes in cell morphologies. RNA and protein for Fc gamma receptor and SRA were transiently elevated, peaked at 3 days, and returned to basal levels after 1 week. In contrast, microglia remained significantly activated through the 28-day time point, as determined by CD45 and complement receptor 3 levels. These findings indicate a multivariate response to LPS, and evaluation of microglial phenotypes may lead to a better understanding of neuroinflammatory diseases. (c) 2005 Wiley-Liss, Inc.