Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance
Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance
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DOI：
10.1523/jneurosci.4814-07.2008
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发表时间：
2008-04-16
影响因子：
5.3
通讯作者：
Calhoun, Michael E.
中科院分区：
文献类型：
--
作者：
Bolmont, Tristan;Haiss, Florent;Calhoun, Michael E.
在阿尔茨海默病中，小胶质细胞聚集在淀粉样斑块周围，但是，尽管它们具有治疗潜力，但其反应动力学的各个方面以及在斑块发病机制中的作用仍然是假设的。通过在转基因小鼠中使用体内成像和定量形态学测量，我们证明局部驻留小胶质细胞通过延长过程并随后向斑块迁移而对斑块形成快速反应，其中个体转化的小胶质细胞体体在数周内保持空间稳定。与斑块相关的小胶质细胞的数量以每月每个斑块几乎三个的速度增加，与斑块体积无关。较大的斑块被较大的小胶质细胞包围，并且一部分斑块的大小随着时间的推移而变化，其增加或减少与相关小胶质细胞的体积相关。与斑块相关的小胶质细胞远非采取更静态的角色，而是在斑块/胶质细胞界面保留了快速的过程和膜运动。在斑块附近，小胶质细胞以更高的速率内化全身注射的淀粉样蛋白结合染料。这些结果表明小胶质细胞在斑块维持中的作用，并为治疗干预提供了具有多个目标的模型。
Microglial cells aggregate around amyloid plaques in Alzheimer's disease, but, despite their therapeutic potential, various aspects of their reactive kinetics and role in plaque pathogenesis remain hypothetical. Through use of in vivo imaging and quantitative morphological measures in transgenic mice, we demonstrate that local resident microglia rapidly react to plaque formation by extending processes and subsequently migrating toward plaques, in which individual transformed microglia somata remain spatially stable for weeks. The number of plaque-associated microglia increased at a rate of almost three per plaque per month, independent of plaque volume. Larger plaques were surrounded by larger microglia, and a subset of plaques changed in size over time, with an increase or decrease related to the volume of associated microglia. Far from adopting a more static role, plaque-associated microglia retained rapid process and membrane movement at the plaque/glia interface. Microglia internalized systemically injected amyloid-binding dye at a much higher rate in the vicinity of plaques. These results indicate a role for microglia in plaque maintenance and provide a model with multiple targets for therapeutic intervention.