Student Jeju National University, Republic of Korea
Abstract: Chronic stress has been implicated in the etiology of neurodegenerative disorders such as Alzheimer’s disease (AD) and brain aging, primarily by disrupting the hypothalamus-pituitary-adrenal (HPA) axis. This dysfunction leads to hyperactivation of the HPA axis, resulting in elevated glucocorticoid levels, which are commonly observed in AD patients. However, individual responses to stress vary, with stress-resilient individuals showing no significant neurodegenerative phenotypes with normalized HPA axis despite similar stress exposure. Thus, identifying the stress resilience targets that contribute to stress resilience under diverse stress conditions, including prenatal and adulthood stress, is crucial for developing targeted therapeutic strategies for AD and brain aging. In this study, we used a chronic unpredictable mild stress (CUMS) protocol in a mouse to distinguish between stress-resilient and stress-susceptible groups. Mice were exposed to either prenatal or adult stress, and their cognitive and depressive-like behaviors were assessed. Resilient mice exhibited normal cognition and mood. We then performed RNA sequencing of the brain to identify potential resilience genes. Furthermore, we also performed amplicon sequencing and LC/MS on stool to find the potential resilience-related microbiome. Our findings highlight the importance of stress resilience targets in modulating the effects of chronic stress on neurodegeneration. The significance of these genes or molecules is being further validated in AD models.
Funding Source: National Research Foundation of Korea grant funded by the Korea government (MSIT) (RS-2024-00345307) Korea Basic Science Institute (National Research Facilities and Equipment Center) grant funded by the MSIT (RS-2024-00403028)
