Summary: Mouse study shows chronic psychological stress reduces new neuron survival in the dentate gyrus of the hippocampus.
Source: Tokyo University of Science
Depression is a major medical and social challenge worldwide. Among the ideas used to explain its biological basis, the “neurogenic hypothesis of depression” has drawn significant interest.
This hypothesis proposes that damage or functional decline in brain regions such as the hippocampus can contribute to depressive disorders. Both physical and psychological stressors can drive such deterioration. While the impact of physical stress on brain structure and mood has been studied extensively, the specific effects of psychological stress on hippocampal neurogenesis remain less clear.
Researchers have recently developed a model of psychological stress in mice called chronic vicarious social defeat stress, where an animal experiences the social defeat of another animal without direct physical confrontation. A team at Tokyo University of Science applied this model to investigate whether emotionally driven stress alters hippocampal neurogenesis and produces depression-like behaviors.
Professor Akiyoshi Saitoh, one of the study’s lead authors, explained the motivation: “The number of people affected by depression is increasing globally, yet the detailed biological mechanisms remain elusive. We focused on how psychological stress might affect adult hippocampal neurogenesis to better understand its role in depressive disorders.”
The work appears in the journal Behavioural Brain Research.
After subjecting mice to prolonged vicarious social defeat stress, Professor Saitoh and colleagues, including Toshinori Yoshioka and Daisuke Yamada, conducted behavioral assessments and histological analyses of the animals’ brains.
Stressed animals displayed behavioral changes consistent with depression models, including social withdrawal. Importantly, the researchers observed a significant reduction in the survival of newly generated neurons in the dentate gyrus region of the hippocampus when compared with unstressed control mice. The dentate gyrus plays a key role in memory formation and processing sensory information.
The decrease in new neuron survival persisted for up to four weeks after the stress period. Notably, the stress paradigm did not alter the rate of cell proliferation, nor did it change the observed differentiation and maturation profiles of the new neurons during the observation window. In other words, stress specifically reduced survival of newborn neurons rather than their birth or developmental progression.
The team also tested whether antidepressant treatment could reverse these effects. Chronic treatment with the selective serotonin reuptake inhibitor fluoxetine restored cell survival rates in stressed mice and improved social behavior, supporting a link between antidepressant action, hippocampal neurogenesis, and behavioral recovery in this model.
Toshinori Yoshioka commented on the findings: “Our results indicate that prolonged psychological stress can impair neurogenesis specifically by reducing the survival of new neurons in the dentate gyrus. We believe this animal model will be valuable for exploring depression’s underlying mechanisms and for developing new therapeutic strategies.”
Overall, this study strengthens the case that emotional stress affects hippocampal structure and function in ways that may contribute to depressive symptoms. By isolating the impact of non-physical social stress on neuronal survival, the research adds clarity to the neurogenic hypothesis and highlights an animal model useful for future investigations into depression and treatment development.
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
Chronic vicarious social defeat stress attenuates new-born neuronal cell survival in mouse hippocampus
Growing evidence links adult hippocampal neurogenesis to the pathophysiology of depressive disorders. Chronic social defeat stress paradigms have become important animal models for depression, showing neural plasticity changes in the hippocampus. Yet the effects of non-physical (psychological) stress on neurogenesis have been less well characterized.
This study examined the chronic vicarious social defeat stress model to determine how psychological stress affects hippocampal neurogenesis in mice. Immediately after the stress period, researchers found a marked reduction in the survival of newborn neurons in the dentate gyrus, while cell proliferation rates remained unchanged.
The reduced survival persisted for four weeks post-stress. Differentiation and maturation markers of the newborn neurons did not differ from control animals. Chronic treatment with the antidepressant fluoxetine reversed social behavior deficits and enhanced newborn neuron survival in stressed mice.
These results indicate that emotional stress in the vicarious social defeat paradigm impairs neuronal survival in the hippocampus, supporting the model’s relevance to studying depression and testing therapeutic interventions.