Brain and Spinal Injury Center, University of California, San Francisco, CA, USA.
Brain Behav Immun. 2012 Jan;26(1):18-23. doi: 10.1016/j.bbi.2011.07.225. Epub 2011 Jul 20.
Growing evidence suggests that adult-born granule cells integrate into hippocampal networks and are required for proper cognitive function. Although neuroinflammation is involved in many disorders associated with cognitive impairment, it remains unknown whether it impacts the recruitment of adult-born neurons into behaviorally relevant hippocampal networks. Under similar behavioral conditions, exploration-induced expression of the immediate-early gene Arc in hippocampal cells has been linked to cellular activity observed by electrophysiological recording. By detecting exploration-induced Arc protein expression, we investigated whether neuroinflammation alters the recruitment of adult-born neurons into behaviorally relevant hippocampal networks. Neuroinflammation was induced in rats by intra-cerebroventricular infusion of lipopolysaccharide for 28 days. Animals received bromodeoxyuridine injections starting on day 29 (5 days) and were euthanized two months later. Persistent lipopolysaccharide-induced neuroinflammation was reliably detected by microglial activation in the hippocampus. Neuroinflammation did not impact the number of adult-born neurons but did alter their migration pattern through the granule cell layer. There was a positive correlation between the density of activated microglia and alterations in the fraction of existing granule neurons expressing Arc, suggesting that neuroinflammation induced a long-term disruption of hippocampal network activity. The proportion of adult-born neurons expressing behaviorally induced Arc was significantly lower in lipopolysaccharide-treated rats than in controls. This observation supports the fact that neuroinflammation significantly impacts adult-born neurons recruitment into hippocampal networks encoding spatial information.
越来越多的证据表明，成年产生的颗粒细胞整合到海马网络中，并且对于适当的认知功能是必需的。尽管神经炎症参与了许多与认知障碍相关的疾病，但尚不清楚它是否会影响成年产生的神经元进入与行为相关的海马网络的招募。在类似的行为条件下，海马细胞中即时早期基因 Arc 的探索诱导表达与电生理记录观察到的细胞活动有关。通过检测探索诱导的 Arc 蛋白表达，我们研究了神经炎症是否改变成年产生的神经元进入与行为相关的海马网络的招募。通过在 28 天内向脑室内输注脂多糖来诱导神经炎症。动物从第 29 天（5 天）开始接受溴脱氧尿苷注射，并在两个月后安乐死。海马中小胶质细胞的激活可靠地检测到持续的脂多糖诱导的神经炎症。神经炎症不会影响成年产生的神经元的数量，但会改变它们通过颗粒细胞层的迁移模式。活化的小胶质细胞的密度与现有的颗粒神经元表达 Arc 的分数的变化之间存在正相关，这表明神经炎症诱导了海马网络活动的长期破坏。在脂多糖处理的大鼠中，表达行为诱导的 Arc 的成年产生的神经元的比例明显低于对照组。这一观察结果支持这样一个事实，即神经炎症显著影响成年产生的神经元进入编码空间信息的海马网络的招募。
