“Second-hand” psychological stress can lead to depression in mice, finds study

Depression is a serious medical condition that plagues modern society. Several theories have been proposed to explain the physiological basis of depression, of which the “neurogenic hypothesis of depression” has garnered much attention. The theory follows that deterioration in brain regions, like hippocampus, can result in depression. This deterioration can be caused by physical and psychological stress. While the depressive effects of physical stress have been well studied, little is known about psychological stress in this regard.

Recent research has explained how vicarious social defeat can cause psychological stress in mice. This involves the mouse being made to experience defeat of another mouse in an experimental social setting. Using this model, a group of scientists from Japan attempted to establish a link between depressive symptoms and hippocampal neurogenesis.

Prof. Akiyoshi Saitoh from Tokyo University of Science, one of the lead authors of the study, further explains the motivation behind this research, “The number of individuals suffering from depression has been on the rise the world over. However, the detailed pathophysiology of depression still remains to be elucidated. So, we decided to focus on the possible mechanism of psychological stress in adult hippocampal neurogenesis, to understand its role in depressive disorders.” The study was published in the journal Behavioural Brain Research.

After exposing the mice to chronic vicarious social defeat stress, Prof. Saitoh and the team, including Mr. Toshinori Yoshioka and Dr. Daisuke Yamada from Tokyo University of Science, analyzed their behavior and brains in close detail. Aside from behavioral deficits like social withdrawal, the stressed mice also showed a significant decrease in the survival rate of new-born neurons in the dentate gyrus, a region in the hippocampus responsible for sensory perception and memory, compared to the non-stressed controls. This condition persisted for up to four weeks, after “stressing” the mice. However, cell growth, differentiation, and maturation did not differ between the groups of mice during the period of observation. Notably, the cell survival rate was restored in the stressed mice after treatment with a chronic antidepressant called fluoxetine.

Regarding the results, Mr. Toshinori Yoshioka adds, “We have found out that chronic mental stress affects the neurogenesis of the hippocampal dentate gyrus. Also, we believe that this animal model will play an important role in elucidating the pathophysiology of depression, and in the development of corresponding novel drug.”

Overall, this study has provided important insights into the pathophysiology of depression. Also, it goes without saying how this study paves the way for future research into the role of psychological stress in depression.

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Reference

DOI: https://doi.org/10.1016/j.bbr.2021.113536

About The Tokyo University of Science

Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan's development in science through inculcating the love for science in researchers, technicians, and educators.  

With a mission of “Creating science and technology for the harmonious development of nature, human beings, and society", TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today's most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.

Website: https://www.tus.ac.jp/en/mediarelations/

About Professor Akiyoshi Saitoh from Tokyo University of Science

Dr. Akiyoshi Saitoh is a Professor at the Faculty of Pharmaceutical Sciences, Tokyo University of Science. A respected and senior researcher with more than 20 years of experience in his chief areas of interest―medicinal pharmacology, behavioral pharmacology, and neuroscience, including the role of the amygdala in the extinction of fear memory in rodents and the development of a novel opioid delta receptor agonist for antidepressants/anxiolytics―he has more than 100 research publications to his credit, and is the lead scientist of this study.

Funding information

This study was supported by Japan Agency for Medical Research and Development, under grant number 17pc0101018h0001.