Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.
Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.
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DOI：
10.1371/journal.pone.0106331
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang TL
中科院分区：
文献类型：
--
作者：
Fu HQ;Yang T;Xiao W;Fan L;Wu Y;Terrando N;Wang TL
炎症是从神经变性到脓毒症的几种疾病状态的标志，但也涉及衰老等生理过程。非消退性炎症和长期神经炎症是与包括衰老在内的几种疾病有关的不清楚的过程。在这项研究中，我们研究了内毒素血症的长期影响，全身脂多糖（LPS）注射，重点是星形胶质细胞激活和细胞因子释放的作用，在老龄大鼠的大脑。老年大鼠腹腔注射LPS（2 mg/kg）或0.9%生理盐水。检测海马组织和全身促炎细胞因子（TNFα和IL-1β）水平和NF-κB p65活化。通过双重免疫荧光染色在不同时间点检测CNS中的星形胶质细胞和细胞因子释放，直至第30天。注射LPS后30分钟（p<0.001）和6小时（p <0.001），血清TNFα和IL-1β水平显著升高。在中枢，LPS处理的大鼠表现出上调的mRNA表达和蛋白水平的促炎细胞因子在海马。这些变化与海马齿状回（DG）星形胶质细胞增生、IL-1β免疫反应性和NF-κB p65表达升高相关，直至LPS暴露后30天。总的来说，这些数据表明，LPS诱导老年大鼠海马神经炎症和星形胶质细胞活化延长。海马NF-κB p65和星形胶质细胞源性IL-1β过度释放可能在调节持久的神经炎症中起关键作用。
Inflammation is a hallmark of several disease states ranging from neurodegeneration to sepsis but is also implicated in physiological processes like ageing. Non-resolving inflammation and prolonged neuroinflammation are unclear processes implicated in several conditions, including ageing. In this study we studied the long-term effects of endotoxemia, as systemic lipopolysaccharide (LPS) injection, focusing on the role of astrocyte activation and cytokine release in the brain of aged rats. A single dose of LPS (2 mg/kg) or 0.9% saline was injected intraperitoneally in aged rats. Levels of pro-inflammatory cytokines (TNFα and IL-1β) and NF-κB p65 activation were measured systemically and in hippocampal tissue. Astrocytes and cytokines release in the CNS were detected via double immunofluorescence staining at different time-points up to day 30. Serum levels of TNFα and IL-1β were significantly increased acutely after 30 minutes (p<0.001) and up to 6 hours (p<0.001) following LPS-injection. Centrally, LPS-treated rats showed up-regulated mRNA expression and protein levels of pro-inflammatory cytokines in the hippocampus. These changes associated with astrogliosis in the hippocampus dentate gyrus (DG), IL-1β immunoreactivity and elevated NF-κB p65 expression up to day 30 post LPS exposure. Overall, these data demonstrate that LPS induces prolonged neuroinflammation and astrocyte activation in the hippocampus of aged rats. Hippocampal NF-κB p65 and excessive astrocytes-derived IL-1β release may play a pivotal role in regulating long-lasting neuroinflammation.
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