Journal
AUTOPHAGY
Volume 16, Issue 3, Pages 512-530Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2019.1630222
Keywords
Atg7 knockout; autophagic cell death; corticosterone; hippocampal neurogenesis; serum; glucocorticoid regulated kinase 3; stress
Categories
Funding
- National Research Foundation of Korea (NRF) [2017R1A2B4004289, 2018M3C7A1056275]
- KBRI basic research program of the Ministry of Science and ICT of Korea [19-BR-01-08]
- DGIST Convergence Science Center Program of the Ministry of Science and ICT of Korea [19-BD-04]
- National Research Foundation of Korea [2017R1A2B4004289, 2018M3C7A1056275]
- Ministry of Science and ICT of Korea [19-BR-01-08, 19-BD-04]
- National Research Foundation of Korea [2017R1A2B4004289, 2018M3C7A1056275] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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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