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

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dc.contributor.advisor 유성운 -
dc.contributor.author Hyeonjeong Jeong -
dc.date.accessioned 2026-01-23T10:53:49Z -
dc.date.available 2026-01-23T10:53:49Z -
dc.date.issued 2026 -
dc.identifier.uri https://scholar.dgist.ac.kr/handle/20.500.11750/59589 -
dc.identifier.uri http://dgist.dcollection.net/common/orgView/200000946239 -
dc.description Autophagic cell death, Adult hippocampal neural stem cells, Chronic restraint stress, Serum/ glucocorticoid-regulated kinase 3 (SGK3), ULK1 -
dc.description.tableofcontents 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
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dc.format.extent 67 -
dc.language eng -
dc.publisher DGIST -
dc.title Serum/glucocorticoid-regulated kinase 3 mediates autophagic death of adult hippocampal neural stem cells following psychological stress -
dc.type Thesis -
dc.identifier.doi 10.22677/THESIS.200000946239 -
dc.description.degree Doctor -
dc.contributor.department Department of Brain Sciences -
dc.contributor.coadvisor Seong Who Kim -
dc.date.awarded 2026-02-01 -
dc.publisher.location Daegu -
dc.description.database dCollection -
dc.citation XT.BD 정94 202602 -
dc.date.accepted 2026-01-19 -
dc.contributor.alternativeDepartment 뇌과학과 -
dc.subject.keyword Autophagic cell death, Adult hippocampal neural stem cells, Chronic restraint stress, Serum/ glucocorticoid-regulated kinase 3 (SGK3), ULK1 -
dc.contributor.affiliatedAuthor Hyeonjeong Jeong -
dc.contributor.affiliatedAuthor Seong-Woon Yu -
dc.contributor.affiliatedAuthor Seong Who Kim -
dc.contributor.alternativeName 정현정 -
dc.contributor.alternativeName Seong-Woon Yu -
dc.contributor.alternativeName 김승후 -
dc.rights.embargoReleaseDate 2031-02-28 -
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