Summary: Mouse study reveals chronic stress affects neurogenesis in the dentate gyrus.

Source: Tokyo University of Science

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.

While the depressive effects of physical stress have been well studied, little is known about psychological stress in this regard. Image is in the public domain

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.

About this stress and depression research news

Author: Tsutomu Shimizu
Source: Tokyo University of Science
Contact: Tsutomu Shimizu – Tokyo University of Science
Image: The image is in the public domain

Original Research: Closed access.
“Chronic vicarious social defeat stress attenuates new-born neuronal cell survival in mouse hippocampus” by Toshinori Yoshioka et al. Behavioral Brain Research


Abstract

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Chronic vicarious social defeat stress attenuates new-born neuronal cell survival in mouse hippocampus

Increasing evidence has shown that adult hippocampal neurogenesis is closely related to the pathophysiological condition of depressive disorders. Recently, chronic social defeat stress paradigms have been regarded as important animal models of depression, accompanied with neural plastic changes in the hippocampus. However, little is known about influences of non-physical stress on neurogenesis.

In the present study, we focused on the chronic vicarious social defeat stress paradigm and examined the effect of psychological stress on mouse hippocampal neurogenesis. Immediately after the chronic psychological stress, the cell survival rate in the dentate gyrus of the hippocampus was significantly diminished without modifying the cell proliferation rate.

The decreased ratio in cell survival persisted for 4 weeks after the stress-loading period, while the differentiation and maturity of new-born neurons were identical to control groups. Furthermore, treatment with the chronic antidepressant fluoxetine reversed the social behavioral deficits and promoted new-born neurons survival.

These results demonstrate that emotional stress in the vicarious social defeat stress paradigm influences neuronal cell survival in the hippocampus, which reinforces its validity as an animal model of depression.



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