Atg5 in microglia regulates sex-specific effects on postnatal neurogenesis in Alzheimer's disease

被引：0

作者：

Walter, Ellen ^{[1
]}

Angst, Gabrielle ^{[1
,3
,4
,5
,6
]}

Bollinger, Justin ^{[2
]}

Truong, Linh ^{[1
]}

Ware, Elena ^{[1
]}

Wohleb, Eric S. ^{[2
]}

Fan, Yanbo ^{[1
]}

Wang, Chenran ^{[1
,3
,4
,5
,6
]}

机构：

[1] Univ Cincinnati, Coll Med, Dept Canc Biol, Cincinnati, OH 45221 USA

[2] Univ Cincinnati, Coll Med, Dept Pharmacol & Syst Physiol, Cincinnati, OH USA

[3] Ohio State Univ, Arthur G James Canc Hosp, Ohio State Comprehens Canc Ctr, Dept Radiat Oncol, Columbus, OH 43210 USA

[4] Ohio State Univ, Richard J Solove Res Inst, Columbus, OH 43210 USA

[5] Ohio State Univ, Coll Med, Columbus, OH 43210 USA

[6] Ohio State Univ, James Comprehens Canc Ctr, Ctr Canc Metab, Columbus, OH 43210 USA

来源：

NPJ AGING | 2025年 / 11卷 / 01期

关键词：

NEURAL STEM-CELLS; ADULT NEUROGENESIS; HIPPOCAMPAL NEUROGENESIS; INCIDENCE RATES; AUTOPHAGY; ASTROCYTES; MECHANISMS; EXPRESSION; PHYSIOLOGY; DEMENTIA;

D O I：

10.1038/s41514-025-00209-0

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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.

引用

页数：16

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