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Autophagic death of neural stem cells mediates chronic stress-induced decline of adult hippocampal neurogenesis and cognitive deficits

Authors
Jung, SeongheeChoe, SeongwonWoo, HanwoongJeong, HyeonjeongAn, Hyun-KyuMoon, HyewonRyu, Hye YoungYeo, Bo KyoungLee, Ye WonChoi, HyosunMun, Ji YoungSun, WoongChoe, Han KyoungKim, Eun-KyoungYu, Seong-Woon
Issue Date
3-3월-2020
Publisher
TAYLOR & FRANCIS INC
Keywords
Atg7 knockout; autophagic cell death; corticosterone; hippocampal neurogenesis; serum; glucocorticoid regulated kinase 3; stress
Citation
AUTOPHAGY, v.16, no.3, pp.512 - 530
Indexed
SCIE
SCOPUS
Journal Title
AUTOPHAGY
Volume
16
Number
3
Start Page
512
End Page
530
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/57328
DOI
10.1080/15548627.2019.1630222
ISSN
1554-8627
Abstract
Macroautophagy/autophagy is generally regarded as a cytoprotective mechanism, and it remains a matter of controversy whether autophagy can cause cell death in mammals. Here, we show that chronic restraint stress suppresses adult hippocampal neurogenesis in mice by inducing autophagic cell death (ACD) of hippocampal neural stem cells (NSCs). We generated NSC-specific, inducible Atg7 conditional knockout mice and found that they had an intact number of NSCs and neurogenesis level under chronic restraint stress and were resilient to stress- or corticosterone-induced cognitive and mood deficits. Corticosterone treatment of adult hippocampal NSC cultures induced ACD via SGK3 (serum/glucocorticoid regulated kinase 3) without signs of apoptosis. Our results demonstrate that ACD is biologically important in a mammalian system in vivo and would be an attractive target for therapeutic intervention for psychological stress-induced disorders.
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