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

Seonghee Jung, Seongwon Choe, Hanwoong Woo, Hyeonjeong Jeong, Hyun-Kyu An, Hyewon Moon, Hye Young Ryu, Bo Kyoung Yeo, Ye Won Lee, Hyosun Choi, Ji Young Mun, Woong Sun, Han Kyoung Choe, Eun-Kyoung Kim, Seong-Woon Yu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)512-530
Number of pages19
JournalAutophagy
Volume16
Issue number3
Early online date24 Jun 2019
DOIs
Publication statusPublished - 3 Mar 2020
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Atg7 knockout
  • autophagic cell death
  • corticosterone
  • hippocampal neurogenesis
  • serum/glucocorticoid regulated kinase 3
  • stress

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