小胶质细胞中的Atg5调节阿尔茨海默病出生后神经发生的性别特异性作用。

IF 4.1 Q2 GERIATRICS & GERONTOLOGY
Ellen Walter, Gabrielle Angst, Justin Bollinger, Linh Truong, Elena Ware, Eric S Wohleb, Yanbo Fan, Chenran Wang
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引用次数: 0

摘要

与男性阿尔茨海默病患者相比,女性阿尔茨海默病(AD)患者表现出更大的认知缺陷和更严重的AD病理。在本研究中,我们发现雌性小胶质细胞中Atg5的条件敲除(cKO)在常见的AD小鼠模型(5xFAD)中未能获得疾病相关小胶质细胞(DAM)基因特征。接下来,我们分析了Atg5 cKO的5xFAD小鼠海马和室下区(SVZ)神经干细胞(NSCs)的维持和神经发生。我们的数据表明,Atg5 cKO降低了雌性5xFAD小鼠海马内的NSC数量,而不是雄性5xFAD小鼠。然而,在SVZ中,Atg5 cKO仅损害雄性5xFAD小鼠的NSCs。有趣的是,雌性5xFAD;Fip200 cKO小鼠和5xFAD;Atg14 cKO小鼠没有出现NSC缺陷。这些自噬基因cKO 5xFAD小鼠在SVZ中表现出更高的神经发生活性。总之,我们的数据表明,小胶质细胞Atg5在阿尔茨海默病小鼠出生后神经发生中具有性别特异性作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Atg5 in microglia regulates sex-specific effects on postnatal neurogenesis in Alzheimer's disease.

Female Alzheimer's disease (AD) patients display greater cognitive deficits and worse AD pathology as compared to male AD patients. In this study, we found that conditional knockout (cKO) of Atg5 in female microglia failed to obtain disease-associated microglia (DAM) gene signatures in familiar AD mouse model (5xFAD). Next, we analyzed the maintenance and neurogenesis of neural stem cells (NSCs) in the hippocampus and subventricular zone (SVZ) from 5xFAD mice with Atg5 cKO. Our data indicated that Atg5 cKO reduced the NSC number in hippocampus of female but not male 5xFAD mice. However, in the SVZ, Atg5 cKO only impaired NSCs in male 5xFAD mice. Interestingly, female 5xFAD;Fip200 cKO mice and 5xFAD;Atg14 cKO mice did not show NSC defects. These autophagy genes cKO 5xFAD mice exhibited a higher neurogenesis activity in their SVZ. Together, our data indicate a sex-specific role for microglial Atg5 in postnatal neurogenesis in AD mice.

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