A study conducted by DGIST (Daegu Gyeongbuk Institute of Science and Technology) has discovered that chronic stress causes autophagic death of adult hippocampal neural stem cells (NSCs).
In an exclusive interview with Thailand Medical News, Professor Seong-Woon Yu from the Department of Brain and Cognitive Sciences at DGIST commented,” "It is clearly apparent from our study that cognitive defects and mood disorders brought about by stress are through autophagic death of adult hippocampal NSCs in the brain. With further research, we will be able to take a step further toward the development of an effective treatment of psychological disorders such as depression and anxiety. Furthermore, stress-related neurodegenerative diseases including dementia could be also benefited from our study. We hope to be able to develop much faster and more effective mental disease treatments through joint research with the Chinese National Compound Library to develop a SGK3 inhibitor together."
The research team discovered for the first time that chronic stress causes autophagic death of adult hippocampal NSCs. Autophagy or ‘self-eating’ in Greek, is a cellular function to protect cells from unfavorable conditions through digestion and recycling of inner cell materials, whereby cells can remove toxic or old intracellular components and get nutrients and metabolites for survival.
However, autophagy can turn into a self-destruction process under certain unfavourable conditions, leading to autophagic cell death. Autophagic cell death is a form of cell death distinguished from apoptosis by the causative role of autophagy for cell demise. Using NSCs derived from animal models and genetically-modified animal models, the research team discovered that the death of hippocampal NSCs is prevented and normal brain functions are maintained without stress symptoms when Atg7, one of the major autophagic genes, is removed.
The team from DGIST also further examined the mechanism controlling the autophagy induction of NSCs in more depth, proving that SGK3 (serum/glucocorticoid regulated kinase) gene is the trigger for autophagy initiation. Therefore, when SGK3 gene is removed, hippocampal NSCs do not undergo cell death. These findings are expected to open up new strategies for combatting stress-associated neural diseases.
Chronic stress is infamous for its association with various mental diseases such as depression and schizophrenia that have become very serious social problems. Stress can even raise the risk of neurodegenerative diseases, such as Alzheimer's disease. However, the exact mechanisms underlying damage of brain functions have not been well known until this study by DGIST. While the previous animal model studies found that generation of new neurons is much less in stressed animal models, apoptosis, a well-known cell suicide pathway was not found in NSCs, leading to a conclusion that cell death is not related to loss of NSCs the normal manner during stress. The new findings showed instead it was autophagy and not apostosis that was responsible for ‘NSCs cell deaths’.
Reference: Seonghee Jung et al, Autophagic death of neural stem cells mediates chronic stress-induced decline of adult hippocampal neurogenesis and cognitive deficits, Autophagy(2019). DOI: 10.1080/15548627.2019.1630222