Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system
Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system
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DOI：
10.1016/j.bbi.2007.08.014
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发表时间：
2008-03-01
影响因子：
15.1
通讯作者：
Johnson, Rodney W.
中科院分区：
文献类型：
--
作者：
Chen, Jing;Buchanan, Jessica B.;Johnson, Rodney W.
急性认知障碍在老年外周感染患者中很常见，但原因尚不清楚。在这里，我们给老年和年轻小鼠注射大肠杆菌脂多糖（LPS）来模拟急性外周感染，并通过激光捕获显微解剖从周围的海马组织中分离海马神经元细胞层，并测量几种已知会破坏认知的炎症细胞因子（IL-1 β， IL-6和TNF α）的mRNA。结果显示，与年轻小鼠相比，老年小鼠在LPS后海马的炎症反应增加。免疫组织化学进一步显示，老年小鼠海马中的小胶质细胞比青壮年多，lps处理的老年小鼠齿状回和CA1、CA2和CA3区域中的IL-1 β阳性细胞比青壮年多。在一项要求动物有效地将新信息与先前存在的图式整合以完成空间任务的认知测试中，我们发现，当外围先天免疫系统受到刺激时，老年动物的海马加工过程比年轻动物更容易被破坏。总的来说，研究结果表明，衰老可能会促进与外周感染相关的神经行为并发症，这可能是通过允许炎症细胞因子在调节认知处理的大脑区域过度表达来实现的。(c) 2007爱思唯尔公司版权所有。
Acute cognitive disorders are common in elderly patients with peripheral infections but it is not clear why. Here, we injected old and Young mice with Escherichia coli lipopolysaccharide (LPS) to mimic an acute peripheral infection and separated the hippocampal neuronal cell layers from the surrounding hippocampal tissue by laser capture microdissection and measured mRNA for several inflammatory cytokines (IL-1 beta, IL-6, and TNF alpha) that are known to disrupt cognition. The results showed that old mice had an increased inflammatory response in the hippocampus after LPS compared to younger cohorts. Immunohistochemistry further showed more microglial cells in the hippocampus of old mice compared to young adults, and that more IL-1 beta-positive cells were present in the dentate gyrus and in the CA1, CA2, and CA3 regions of LPS-treated old mice compared to young adults. In a test of cognition that required animals to effectively integrate new information with a preexisting schema to complete a spatial task, we found that hippocampal processing is more easily disrupted in old animals than in younger ones when the peripheral innate immune system is stimulated. Collectively, the results suggest that aging can facilitate neurobehavioral complications associated with peripheral infections probably by allowing the over expression of inflammatory cytokines in brain areas that mediate cognitive processing. (c) 2007 Elsevier Inc. All rights reserved.