Repression of telomere-associated genes by microglia activation in neuropsychiatric disease.

Repression of telomere-associated genes by microglia activation in neuropsychiatric disease.
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DOI:
10.1007/s00406-016-0750-1
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发表时间:
2017-08
影响因子:
4.7
通讯作者:
Gertz K
Gertz K
中科院分区:
医学2区
文献类型:
--
作者:
Kronenberg G;Uhlemann R;Schöner J;Wegner S;Boujon V;Deigendesch N;Endres M;Gertz K

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小胶质细胞衰老可能促进神经精神疾病。这促使我们研究小胶质细胞激活状态和端粒生物学之间的关系。一组与端粒维持、线粒体生物发生和细胞周期调控相关的候选基因在体外M1和M2极化小胶质细胞以及来自中风、阿尔茨海默病和慢性应激模型的MACS纯化的CD 11b+小胶质细胞/脑巨噬细胞中进行了研究。M1极化,缺血和阿尔茨海默病的病理引起了惊人的相似的转录组学的配置文件,特别是,减少表达的小鼠Tert。我们的研究结果将经典的小胶质细胞激活与端粒相关基因的抑制联系起来,提示了小胶质细胞功能障碍的新机制。
Microglia senescence may promote neuropsychiatric disease. This prompted us to examine the relationship between microglia activation states and telomere biology. A panel of candidate genes associated with telomere maintenance, mitochondrial biogenesis, and cell-cycle regulation were investigated in M1- and M2-polarized microglia in vitro as well as in MACS-purified CD11b+ microglia/brain macrophages from models of stroke, Alzheimer’s disease, and chronic stress. M1 polarization, ischemia, and Alzheimer pathology elicited a strikingly similar transcriptomic profile with, in particular, reduced expression of murine Tert. Our results link classical microglia activation with repression of telomere-associated genes, suggesting a new mechanism underlying microglia dysfunction.
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