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Microglia turnover with aging and in an Alzheimer's model via long-term in vivo single-cell imaging
Nature Neuroscience ( IF 25.0 ) Pub Date : 2017-08-28 00:00:00 , DOI: 10.1038/nn.4631
Petra Füger , Jasmin K Hefendehl , Karthik Veeraraghavalu , Ann-Christin Wendeln , Christine Schlosser , Ulrike Obermüller , Bettina M Wegenast-Braun , Jonas J Neher , Peter Martus , Shinichi Kohsaka , Martin Thunemann , Robert Feil , Sangram S Sisodia , Angelos Skodras , Mathias Jucker

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:

通过长期体内单细胞成像,小胶质细胞衰老与衰老并在阿尔茨海默氏症模型中

为了阐明小胶质细胞在脑稳态和疾病中的作用,必须了解它们的维持,增殖和更新​​。然而,脑小胶质细胞的寿命仍然不确定,并且反映了早期评估中主要是间接的混杂因素。我们在活着的小鼠中对单个驻留小胶质细胞进行了基因标记,然后使用多光子显微镜随着时间的推移来监视这些细胞。在稳态条件下,我们发现新皮层居民小胶质细胞寿命长,中位寿命超过15个月。因此,这些细胞中大约有一半会在整个小鼠寿命中幸存下来。尽管在稳态条件下常驻新皮层小胶质细胞的增殖低,但在阿尔茨海默氏病的β-淀粉样变性小鼠模型中,小胶质细胞的增殖增加了三倍。
更新日期:2017-09-28
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