Title

Serum/glucocorticoid-regulated kinase 3 mediates autophagic death of adult hippocampal neural stem cells following psychological stress

DGIST Authors

Hyeonjeong Jeong ; Seong-Woon Yu ; Seong Who Kim

Advisor

유성운

Co-Advisor(s)

Seong Who Kim

Issued Date

2026

Awarded Date

2026-02-01

Type

Thesis

Description

Autophagic cell death, Adult hippocampal neural stem cells, Chronic restraint stress, Serum/ glucocorticoid-regulated kinase 3 (SGK3), ULK1

Table Of Contents

Ⅰ. General Introduction 1
1.1 Adult neurogenesis 1
1.1.1 Adult NSCs and adult neurogenesis 1
1.1.2 Adult neurogenesis and stress 5
1.1.3 Hippocampal neurogenesis and antidepressants 8
1.2 Programmed cell death 9
1.2.1 Apoptosis 9
1.2.2 Autophagy and ACD 10
1.2.3 Necroptosis 13
1.3 ACD in ahNSCs 14

ⅠI. Materials and Methods 16
2.1 Animals and CRS procedure 16
2.2 Antibodies and reagents 16
2.3 Constructs 17
2.4 Immunofluorescence staining 17
2.5 Golgi-Cox staining 18
2.6 Stereological cell counting 18
2.7 Behavior test 18
2.8 Serum CORT level measurement 19
2.9 Laboratory Behavior Observation Registration and Analysis System (LABORAS) test (automated 24-h activity monitoring) 19
2.10 Cell culture 19
2.11 Cell death assay 19
2.12 Western blotting 19
2.13 Co-immunoprecipitation (Co-IP) 20
2.14 Generation of stable knockdown or knockout ahNSC cells 20
2.15 Pull-down assay 20
2.16 In vitro kinase assay 21
2.17 qRT-PCR 21
2.18 LC-MS/MS 21
2.19 Statistics 22

ⅠII. Neural stem cell-specific deletion of Atg7 alleviates hippocampal dysfunction and neuronal alterations induced by CRS 23
3.1 Introduction 23
3.2 Results 24

IV. Serum/glucocorticoid-regulated kinase 3 mediates psychological stress-induced autophagic death in adult hippocampal neural stem cells by interacting and stabilizing ULK1 29
4.1 Introduction 29
4.2 Results 31
4.2.1 ahNSCs are preserved under CRS in Sgk3NSC cKO mice. 31
4.2.2 CRS-induced hippocampal dysfunctions are prevented in Sgk3NSC cKO mice. 34
4.2.3 SGK3 regulates ULK1 stability and its interaction with ATG13. 36
4.2.4 SGK3 induces ACD via ULK1 phosphorylation following CORT treatment 40
4.2.5 ULK1 T10 phosphorylation by SGK3 is essential for ULK1 stability and ACD induction. 42
4.2.6 Pharmacological inhibition of SGK3 attenuates CORT-induced ACD. 44
4.2.7 SGK3i reduces ULK1 stability and its interaction with ATG13, resulting in suppression of CORT-induced ACD. 47
4.2.8 Pharmacologic inhibition of SGK3 blocks CRS-induced reduction of NSCs and hippocampal dysfunctions. 50

V. General Discussion 54

VI. References 57

Abstract in Korean 67

URI

https://scholar.dgist.ac.kr/handle/20.500.11750/59589
http://dgist.dcollection.net/common/orgView/200000946239

DOI

10.22677/THESIS.200000946239

Degree

Doctor

Department

Department of Brain Sciences

Publisher

DGIST

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