Age-related alterations in the dynamic behavior of microglia.
Age-related alterations in the dynamic behavior of microglia.
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DOI：
10.1111/j.1474-9726.2010.00660.x
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发表时间：
2011-04
期刊：
影响因子：
7.8
通讯作者：
Wong WT
中科院分区：
文献类型：
--
作者：
Damani MR;Zhao L;Fontainhas AM;Amaral J;Fariss RN;Wong WT
小胶质细胞是中枢神经系统的主要驻留免疫细胞，表现出涉及快速过程运动和细胞迁移的动态行为，这被认为是免疫监视和组织修复关键功能的基础。尽管小胶质细胞激活的与年龄相关的变化与衰老神经退行性疾病的发病机制有关，但小胶质细胞的动态行为如何受到衰老的影响尚不完全清楚。在这项研究中，我们采用视网膜小胶质细胞原位实时成像来比较年轻和老年动物的小胶质细胞形态和行为动力学。我们发现，处于静息状态的老化小胶质细胞具有明显更小、分支更少的树突乔木，并且过程运动也更慢，这可能会损害它们持续调查和与环境相互作用的能力。我们还发现，小胶质细胞对损伤的动态反应与年龄有关。年轻的小胶质细胞通过增加其运动性并变得更加分支来对细胞外 ATP（一种与损伤相关的信号）作出反应，而衰老的小胶质细胞则表现出相反的反应，变得不那么动态和分支。为了响应激光引起的局灶性组织损伤，与年轻的小胶质细胞相比，衰老的小胶质细胞表现出较慢的急性反应，过程运动和细胞迁移率较低。有趣的是，衰老的小胶质细胞从损伤部位解聚的长期反应被延迟，这表明衰老的小胶质细胞反应虽然启动较慢，但更持久。总之，小胶质细胞在休息和受伤后行为的这些改变特征揭示了中枢神经系统中年龄依赖性免疫反应的失调，这可能说明小胶质细胞对年龄相关的神经炎症变性的贡献。
Microglia, the primary resident immune cells of the CNS, exhibit dynamic behavior involving rapid process motility and cellular migration that is thought to underlie key functions of immune surveillance and tissue repair. Although age-related changes in microglial activation have been implicated in the pathogenesis of neurodegenerative diseases of aging, how dynamic behavior in microglia is influenced by aging is not fully understood. In this study, we employed live imaging of retinal microglia in situ to compare microglial morphology and behavioral dynamics in young and aged animals. We found that aged microglia in the resting state have significantly smaller and less branched dendritic arbors, and also slower process motilities, which likely compromise their ability to continuously survey and interact with their environment. We also found that dynamic microglial responses to injury were age-dependent. While young microglia responded to extracellular ATP, an injury-associated signal, by increasing their motility and becoming more ramified, aged microglia exhibited a contrary response, becoming less dynamic and ramified. In response to laser-induced focal tissue injury, aged microglia demonstrated slower acute responses with lower rates of process motility and cellular migration compared to young microglia. Interestingly, the longer term response of disaggregation from the injury site was retarded in aged microglia, indicating that senescent microglial responses, while slower to initiate, are more sustained. Together, these altered features of microglial behavior at rest and following injury reveal an age-dependent dysregulation of immune response in the CNS that may illuminate microglial contributions to age-related neuroinflammatory degeneration.
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影响因子：
3.3
作者：
LAWSON, LJ;PERRY, VH;GORDON, S
通讯作者：
GORDON, S
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR
衰老大脑中的小胶质细胞：与神经退行性变的相关性
影响因子：
15.1
作者：
Luo XG;Ding JQ;Chen SD
通讯作者：
Chen SD
影响因子：
4.4
作者：
Kaneko, Hiroki;Nishiguchi, Koji M.;Terasaki, Hiroko
通讯作者：
Terasaki, Hiroko
影响因子：
30.8
作者：
Lee, CK;Weindruch, R;Prolla, TA
通讯作者：
Prolla, TA