Review: microglia of the aged brain: primed to be activated and resistant to regulation.
Review: microglia of the aged brain: primed to be activated and resistant to regulation.
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DOI：
10.1111/j.1365-2990.2012.01306.x
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发表时间：
2013-02
影响因子：
5
通讯作者：
Godbout JP
中科院分区：
文献类型：
--
作者：
Norden DM;Godbout JP
中枢神经系统（CNS）内的先天免疫主要由常驻小胶质细胞提供。小胶质细胞是免疫监视的关键，也促进免疫系统和大脑之间的协调反应。例如，小胶质细胞解释并传播在外周中启动的炎症信号。这种短暂的小胶质细胞激活有助于在外周感染后产生适当的生理和行为反应。然而，随着正常衰老，小胶质细胞发展出更多的炎症表型。例如，在几种衰老模型中，大脑中的促炎细胞因子增加，小胶质细胞上的炎症受体表达增加。这种随着年龄增长而增加的小胶质细胞炎症状态被称为引发、反应性或致敏。CNS炎症特征的适度增加和衰老中小胶质细胞功能的改变具有行为和认知后果。尽管如此，当免疫系统受到挑战并且小胶质细胞被激活时，年轻人和老年人之间的小胶质细胞生物学存在重大差异。在这种情况下，与成年人相比，老年人大脑中的小胶质细胞激活被放大和延长。这种放大的小胶质细胞激活的原因可能与随着年龄的增长，几个关键的调节系统的损伤有关，这使得解决小胶质细胞激活变得更加困难。免疫攻击后调节受损和小胶质细胞过度活化的后果是夸大的神经炎症、疾病行为、抑郁样行为和认知缺陷。因此，本综述的目的是讨论目前的理解与年龄相关的小胶质细胞启动，启动和反应性的后果，以及可能导致这些年龄相关的缺陷的调节系统的损害。
Innate immunity within the central nervous system (CNS) is primarily provided by resident microglia. Microglia are pivotal in immune surveillance and also facilitate the coordinated responses between the immune system and the brain. For example, microglia interpret and propagate inflammatory signals that are initiated in the periphery. This transient microglial activation helps mount the appropriate physiological and behavioral response following peripheral infection. With normal aging, however, microglia develop a more inflammatory phenotype. For instance, in several models of aging there are increased pro-inflammatory cytokines in the brain and increased expression of inflammatory receptors on microglia. This increased inflammatory status of microglia with aging is referred to as primed, reactive, or sensitized. A modest increase in the inflammatory profile of the CNS and altered microglial function in aging has behavioral and cognitive consequences. Nonetheless, there are major differences in microglial biology between young and old age when the immune system is challenged and microglia are activated. In this context, microglial activation is amplified and prolonged in the aged brain compared to adults. The cause of this amplified microglial activation may be related to impairments in several key regulatory systems with age that make it more difficult to resolve microglial activation. The consequences of impaired regulation and microglial hyper-activation following immune challenge are exaggerated neuroinflammation, sickness behavior, depressive-like behavior and cognitive deficits. Therefore the purpose of this review is to discuss the current understanding of age-associated microglial priming, consequences of priming and reactivity, and the impairments in regulatory systems that may underlie these age-related deficits.
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影响因子：
4.2
作者：
Bachstetter, Adam D.;Morganti, Josh M.;Jernberg, Jennifer;Schlunk, Andrea;Mitchell, Staten H.;Brewster, Kaelin W.;Hudson, Charles E.;Cole, Michael J.;Harrison, Jeffrey K.;Bickford, Paula C.;Gemma, Carmelina
通讯作者：
Gemma, Carmelina
影响因子：
15.1
作者：
Chen, Jing;Buchanan, Jessica B.;Johnson, Rodney W.
通讯作者：
Johnson, Rodney W.
影响因子：
4.8
作者：
Clarke, Rachael M.;Lyons, Anthony;Lynch, Marina A.
通讯作者：
Lynch, Marina A.
影响因子：
6
作者：
Broderick, C;Hoek, RM;Dick, AD
通讯作者：
Dick, AD
影响因子：
15.1
作者：
Abraham, Jayne;Johnson, Rodney W.
通讯作者：
Johnson, Rodney W.