https://scholar.dgist.ac.kr/handle/20.500.11750/283 2026-04-04T13:36:03Z https://scholar.dgist.ac.kr/handle/20.500.11750/59942 Title: Presenilin 2 regulates corticosterone-induced autophagic death of adult hippocampal neural stem cells Author(s): Hong, Jihyun; An, Hyun-Kyu; Nam, Hyeri; Choi, Jieun; Yu, Seong-Woon Abstract: Chronic psychological stress is a well-known risk factor for neurodegenerative diseases including Alzheimer disease (AD), yet the underlying mechanisms remain unclear. We previously showed that chronic stress impairs adult hippocampal neurogenesis by triggering autophagic cell death of adult hippocampal neural stem (HCN) cells. Impairment of adult hippocampal neurogenesis is widely observed in the brains of human AD patients and animal models. However, it remains unknown whether stress-induced death of HCN cells is related to the pathogenesis of AD. In this study, we investigated whether the stress hormone, corticosterone (CORT) induces HCN cell death through presenilin 2 (Psen2), a gene associated with familial AD. Using CRISPR/Cas9-based knockout models and in vitro CORT treatment, we found that Psen2 expression is upregulated by CORT and Psen2 deletion prevents CORT-induced death in HCN cells. However, the Psen2 N141I mutation, despite its pathogenicity in AD, did not exacerbate CORT-induced cell death in vitro and hippocampus-dependent behavioral deficits in vivo. These findings indicate that while Psen2 is essential for stress-induced death of HCN cells, the Psen2 N141I mutation alone may not be sufficient to link chronic stress to AD pathogenesis. 2025-11-30T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/58961 Title: Anti-depressant effects of a human telomerase-derived peptide GV1001 in an animal model of chronic restraint stress Author(s): Kim, Dayoung; Lee, Younghwan; Kim, Sangjae; Yu, Seong-Woon Abstract: Depression is a common cause of mental illness in the modern world, and the wide variation in symptoms makes it difficult to develop suitable antidepressants. The commonly used serotonin reuptake inhibitors (SSRIs) cause many side effects, making it imperative to develop alternative treatments. GV1001, a 16-amino acid peptide derived from human telomerase reverse transcriptase, has shown various neuroprotective effects in recent studies. However, its effects on depression were unknown. In this study, we found that the administration of GV1001 rescued cognitive deficits, anxiety-, and depressive-like behaviors in a mouse model of chronic restraint stress (CRS). GV1001 efficiently reduced the increased serum corticosterone level and suppressed activation of the hypothalamic CRH neurons, suggesting the modulation of the hypothalamus-pituitary-adrenal axis. Collectively, our findings provide evidence for a novel antidepressant efficacy of GV1001. 2025-09-30T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/58255 Title: Neural stem cell-specific deletion of Atg7 alleviates hippocampal dysfunction and neuronal alterations induced by chronic restraint stress Author(s): Jeong, Hyeonjeong; Choe, Seongwon; Jung, Seonghee; Yu, Seong-Woon Abstract: Adult hippocampal neurogenesis is inhibited by chronic psychological stress and impaired neurogenesis underlies stress-related psychological disorders. We previously reported that chronic restraint stress (CRS) evokes autophagic death of adult hippocampal neural stem cells (NSCs) while NSC-specific deletion of Atg7 prevents death of NSCs. Examination of cognitive ability and mood regulation next day of the termination of stress showed normal hippocampal function in mice deficient of Atg7. However, it was not investigated whether the preservation of NSC pool alleviates hippocampal neuronal alterations. Here, we show that CRS increased c-Fos-positive, activated neurons in the granule cell layer and decreased spine density of CA3 neurons in the hippocampus, and these hippocampal neuronal deficits were prevented by NSC-specific deletion of Atg7. Of note, our observation was conducted right after the termination of CRS. Therefore, our results suggest that the detrimental effects of stress on hippocampal neurons can be buffered by NSCs independent of neurogenesis and NSCs are essential to the hippocampal function both through the neurogenesis-dependent developmental process and by direct regulation of neural activation. 2025-02-28T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/57122 Title: Chronic unpredictable stress induces autophagic death of adult hippocampal neural stem cells Author(s): Choe, Seongwon; Hwang, Hyeonjeong; Choi, Jieun; Yu, Seong-Woon Abstract: Chronic psychological stress is a critical factor for neurological complications like anxiety disorders, dementia, and depression. Our previous results show that chronic restraint stress causes cognitive deficits and mood dysregulation by inducing autophagic death of adult hippocampal neural stem cells (NSCs). However, it is unknown whether other models of psychological stress also induce autophagic death of adult hippocampal NSCs. Here, we show that chronic unpredictable stress (CUS) for 10 days impaired memory function and increased anxiety in mice. Immunohistochemical staining with SOX2 and KI67 revealed a significant reduction in the number of NSCs in the hippocampus following exposure to CUS. However, these deficits were prevented by NSC-specific, inducible conditional deletion of Atg7. These findings suggest that autophagic death of adult hippocampal NSCs is a critical pathogenic mechanism underlying stress-induced brain disorders. © The Author(s) 2024. 2024-05-31T15:00:00Z