To clarify the role of microglia in brain homeostasis and disease, an understanding of their maintenance, proliferation and turnover is essential. The lifespan of brain microglia, however, remains uncertain, and reflects confounding factors in earlier assessments that were largely indirect. We genetically labeled single resident microglia in living mice and then used multiphoton microscopy to monitor these cells over time. Under homeostatic conditions, we found that neocortical resident microglia were long-lived, with a median lifetime of well over 15 months; thus, approximately half of these cells survive the entire mouse lifespan. While proliferation of resident neocortical microglia under homeostatic conditions was low, microglial proliferation in a mouse model of Alzheimer's β-amyloidosis was increased threefold. The persistence of individual microglia throughout the mouse lifespan provides an explanation for how microglial priming early in life can induce lasting functional changes and how microglial senescence may contribute to age-related neurodegenerative diseases.

中文翻译：

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通过长期的体内单细胞成像，随着衰老和阿尔茨海默病模型的小胶质细胞周转。

为了阐明小胶质细胞在脑稳态和疾病中的作用，了解它们的维持、增殖和更新​​是必不可少的。然而，脑小胶质细胞的寿命仍然不确定，并反映了早期评估中主要是间接的混杂因素。我们对活小鼠中的单个常驻小胶质细胞进行基因标记，然后使用多光子显微镜随着时间的推移监测这些细胞。在稳态条件下，我们发现新皮质常驻小胶质细胞寿命长，中位寿命超过 15 个月；因此，这些细胞中约有一半能在小鼠的整个生命周期中存活下来。虽然稳态条件下常驻新皮质小胶质细胞的增殖较低，但阿尔茨海默氏 β-淀粉样变性小鼠模型中的小胶质细胞增殖增加了三倍。