Aging, microglial cell priming, and the discordant central inflammatory response to signals from the peripheral immune system
Aging, microglial cell priming, and the discordant central inflammatory response to signals from the peripheral immune system
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DOI：
10.1189/jlb.0208108
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发表时间：
2008-10-01
影响因子：
5.5
通讯作者：
Johnson, Rodney W.
中科院分区：
文献类型：
--
作者：
Dilger, Ryan N.;Johnson, Rodney W.
最近的研究表明，外周免疫系统的激活会引起不协调的中枢（即，在大脑中）炎症反应，但在其他方面健康的老年人与年轻的队列相比。老年大脑中小胶质细胞反应状态的根本差异被认为是这种不协调炎症反应的基础。因此，衰老过程似乎充当小胶质细胞的“启动”刺激，并且在用触发刺激（即，外周信号传播感染），这些引发的小胶质细胞释放过量的促炎细胞因子。随后，这种过度的细胞因子释放诱发了过度的行为变化，包括厌食、嗜睡、嗜睡、社会互动减少以及认知和运动功能缺陷（统称为疾病行为综合征）。而这种主机优先级的重组通常是适应年轻的科目，有一种倾向，这种反应是适应不良的老年受试者，导致更严重的疾病行为综合征和持续时间。因此，老年受试者中认知障碍的急性发作增加了不良自我护理行为的可能性（即，厌食、体重减轻、不依从），这最终导致更高的住院率和死亡率。
Recent studies suggest that activation of the peripheral immune system elicits a discordant central (i.e., in the brain) inflammatory response in aged but otherwise healthy subjects compared with younger cohorts. A fundamental difference in the reactive state of microglial cells in the aged brain has been suggested as the basis for this discordant inflammatory response. Thus, the aging process appears to serve as a "priming" stimulus for microglia, and upon secondary stimulation with a triggering stimulus (i.e., peripheral signals communicating infection), these primed microglia release excessive quantities of proinflammatory cytokines. Subsequently, this exaggerated cytokine release elicits exaggerated behavioral changes including anorexia, hypersomnia, lethargy, decreased social interaction, and deficits in cognitive and motor function (collectively known as the sickness behavior syndrome). Whereas this reorganization of host priorities is normally adaptive in young subjects, there is a propensity for this response to be maladaptive in aged subjects, resulting in greater severity and duration of the sickness behavior syndrome. Consequently, acute bouts of cognitive impairment in elderly subjects increase the likelihood of poor self-care behaviors (i.e., anorexia, weight loss, noncompliance), which ultimately leads to higher rates of hospitalization and mortality.