Study Uses The Hippocampus Of A Mouse To Help Explain Stress In Humans

A new study published in the Journal of Behavioural Brain Research looked at how chronic vicarious social defeat stress (cVSDS) attenuates newborn neuronal cell survival in a mouse hippocampus.

“In the current research, we examined influences of psychological stress on the adult hippocampal neurogenesis, which is assumed to be inseparably connected to the depressive states,” study author Akiyoshi Saitoh told us. “We also thought that, by using psychological stress alone, we could evaluate relation between stress and neurogenesis nearer construction and pathophysiology of human depressive patients.”

Researchers theorized that mice exposed to psychological stress would show depressive-like symptom (avoidance of social interaction) accompanied by decreases in neurogenesis function.

“Our results revealed that cVSDS mice showed an interesting phenotype in that they present a decrease in social interaction behavior, not immediately after the stress loading session, but four weeks after the session,” Saitoh told us. “Then, we hypothesized that deficits of neurogenesis would cause this phenotype because newborn neurons need approximately four weeks to grow, mature and perform adequate functions.”

In earlier studies, although several animal models of depression had been used for an investigation of the relation between depressive states and neurogenesis, those paradigms have a major problem in that physical stress cannot excluded. Therefore, the research team currently attempted to clarify the relation between hippocampal neurogenesis and psychological stress without physical stress.

“We focused on the chronic vicarious social defeat stress (cVSDS) paradigm (Warren et al., 2013), which is an animal model of depression prepared by exposures of psychological stress alone,” Saitoh told us. “The depressed level in cVSDS mice is evaluated with social interaction behaviors, which is generally used in this paradigm. To evaluate neurogenesis status, we used the BrdU labeling technique, which is took in cells in the proliferation stage, and counted BrdU positive cells in the hippocampus. By changing in the timing of BrdU administration, cell proliferation rate and cell surviving rate of new-born neuronal cells is divisible.”

cVSDS mice showed a decrease in social interaction behaviors. This was particularly noticeable at four weeks after the stress session and is consistent with a previous report (Warren et al., 2013). Interestingly, cVSDS reduced newborn neuronal cell survival but not cell proliferation during the stress-loading period, and the decreased ratio was sustained for at least four weeks. This is the first report to demonstrate that psychological stress influences newborn neuronal cell survival, but not cell proliferation. Moreover, a conventional antidepressant, fluoxetine, improves the social interaction behaviors and the neurogenesis deficits.

“To the best of our knowledge, this is the first report that elucidates influences of psychological stress alone on neurogenesis in the preclinical study,” Saitoh told us. “In addition, although a decrease in newborn neuronal cell survival is only proceeded during the stress-loading period, behavioral deficit is not observed immediately after the stress, but four weeks after.”

Saitoh believes the study can suggest that hippocampal neurogenesis might contribute to long-term effects of stress on mental states, for example, how sick leave after an exposure to stress is insufficient to depressive states.

“We proposed that, in today’s stressful society, one of the important measures to reduce major depressive disorder is to remove stress from our circumstance such as school and workspace, so mutual co-operation is now essential,” Saitoh told us. “Furthermore, we also propose that hippocampal neurogenesis could be a potential drug target, so clarifying of the underlying functional mechanism of neurogenesis is highly required.”

The study also reinforced the validity of the cVSDS paradigm as an animal model of depression. Researchers proposed that further clarifying the molecular mechanism of psychological stress and decreased neuronal cell survival observed in this paradigm could play crucial roles in elucidating the pathophysiology of depression and establish appropriate therapy.

 

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