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Scientists discovered how chronic stress causes brain damage

Scientists discovered how chronic stress causes brain damage. Credit: © AlexShadyuk - Depositphotos.

DGIST researchers, led by Professor Seong-Woon Yu’s of the Department of Brain and Cognitive Sciences, have discovered that chronic stress causes autophagic death of adult hippocampal neural stem cells (NSCs). 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 the loss of brain functions in response to chronic stress have yet to be identified. While previous animal studies found that generation of new neurons is substantially reduced in stressed mice, apoptosis, a well-known cell suicide pathway was not found in NSCs, leading to the conclusion that apoptotic cell death is not involved in the loss of NSCs during stress. Thus, the cause of the decline in the generation of new neural cells (neurogenesis) in the adult brain, especially in the hippocampus, has remained elusive.

Professor Yu’s team discovered for the first time that chronic stress causes autophagic death of adult hippocampal NSCs. Autophagy (self-eating in Greek) is a cellular process to protect cells from unfavorable conditions through digestion and recycling of inner cell materials, thereby cells can remove toxic or old intracellular components and get nutrients and metabolites for survival. However, autophagy can turn into a self-destructive process under certain conditions, leading to autophagic cell death, which is distinct from apoptosis. Using the NSCs derived from rodents and genetically-modified mice, the research team discovered that the death of hippocampal NSCs is prevented and normal brain functions are maintained without stress symptoms when a major autophagy gene (Atg7) is deleted.

The research team also further examined the mechanism controlling the autophagy induction of NSCs in more depth, proving that SGK3 (serum/glucocorticoid regulated kinase3) gene is the trigger for autophagy initiation. Therefore, when SGK3 gene is removed, hippocampal NSCs do not undergo cell death and are spared from stress.

Professor Yu said that “It is clear from our study that cognitive defects and mood disorders brought about by stress is through autophagic death of adult hippocampal NSCs. With continuous research, we’ll be able to take a step further toward the development of 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 SGK3 inhibitor together.”

The study is published in the journal Autophagy.


Materials provided by DGIST (Daegu Gyeongbuk Institute of Science and Technology). Content may be edited for clarity, style, and length.


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