Summary: Chronic stress invokes symptoms similar to irritable bowel syndrome in mouse models.
Source: Tokyo University of Science
Irritable bowel syndrome (IBS) is often accompanied by gastrointestinal symptoms in the small and large intestines. IBS has been classified into four subtypes based on stool inconsistency; these are IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed (IBS-M) and IBS unclassified. But there is a lack of understanding in the scientific literature regarding the mechanisms and treatments of IBS. One of the reasons for this lack of knowledge about SCI is the lack of useful experimental animal models.
Over the years, studies have suggested a link between emotional states and gut dysfunction, highlighting the existence and importance of what is known as the “gut-brain axis” in determining our well-being. be emotional and metabolic.
Recently, chronic social defeat stress (cSDS) and chronic vicarious social defeat stress (cVSDS) have been accepted as a model for major depressive disorder (MDD) and post-traumatic stress disorder.
Could cVSDS animal models help us understand IBS in detail? To find out, researchers at Tokyo University of Science (TUS) led by Professor Akiyoshi Saitoh of the Faculty of Pharmaceutical Sciences, TUS, used cVSDS mouse models. Their goal was to understand the effects of prolonged psychological stress on gut conditions.
The team found that mice induced by psychological stress exhibited higher gut transit rates and visceral pain-related behaviors that are hallmarks of IBS.
Their findings were published in Frontiers in Neuroscience.
Elaborating on their study, Professor Saitoh says: “We focused on the cVSDS paradigm and assessed the impact of emotional stress on gut conditions. We further assessed the potential of the paradigm as a novel animal model of IBS. »
In their study, they subjected mice to physical stress or emotional stress, during which the test animals experienced physical aggression or witnessed the aggression for 10 minutes daily for 10 consecutive days.
On day 11, a social interaction test was performed to assess the stress conditions of the test animals. Stress was also estimated by quantification of plasma corticosterone, charcoal meal test, and capsaicin-induced hyperalgesia test in animals. The researchers also assessed the mice for intestinal permeability, pathology, defecation frequency and stool content.
They found that the charcoal transit rate, indicative of passage through the gut, was significantly elevated in emotionally stressed mice compared to unstressed control (naïve) mice. However, the effects were insignificant in mice that experienced physical stress. Defecation frequency and stool water content also increased in mice under emotional stress.
These effects lasted 1 month after the stress load. Moreover, there were no significant differences in disease state and intestinal permeability between naïve and emotionally stressed mice, suggesting no tissue-level changes due to stress.
Professor Saitoh says: “These results suggest that chronic stress in mice causes IBS-D-like symptoms, such as chronic intestinal peristaltic exacerbations and abdominal hyperalgesia, without intestinal damage.”
Interestingly, the researchers found that changes in gut motility in test animals were enhanced when cVSDS mice were treated with keishikashakuyakuto, a kampo drug used clinically for the treatment of IBS.
The study highlights the advantage of the cVSDS paradigm over traditional methods to induce IBS-D-like symptoms through exposure to repeated psychological stress.
Discussing the mechanisms of these effects, Professor Saitoh says: “From the perspective of the gut-brain axis, we suspect that the insular cortex plays an important role in determining the phenotype of emotionally stressed mice. The insular cortex is part of the upper central nervous system controlling digestive functions and is involved in the process of psychological stress management.
In conclusion, this study demonstrates for the first time that psychological stress induced by cVSDS alone can cause IBS-D-like symptoms in mice. Further research could perhaps build on the cSDS and cVSDS paradigms to elucidate pathophysiological conditions and design treatments for IBS.
About this stress research news
Author: Press office
Source: Tokyo University of Science
Contact: Press Office – Tokyo University of Science
Image: Image is in public domain
Original research: Free access.
“Repeated psychological stress, the chronic stress of vicarious social defeat, evokes irritable bowel syndrome-like symptoms in mice” by Toshinori Yoshioka et al. Frontiers in Neuroscience
Repeated psychological stress, chronic vicarious social defeat stress, evokes irritable bowel syndrome-like symptoms in mice
A growing body of evidence has demonstrated that emotional states and gut conditions are interconnected in so-called “gut-brain interactions.” Indeed, many psychiatric disorders are accompanied by gastrointestinal symptoms, such as irritable bowel syndrome (IBS).
However, the functional connection remains elusive, in part because few useful experimental animal models exist.
Here, we focused on a highly validated animal model of stress-induced psychiatric disorders, such as depression, known as chronic vicarious social stress (cVSDS) mouse models, which we prepared using exposure to repeated psychological stress and then examining their intestinal conditions. .
In the charcoal meal test and the capsaicin-induced hyperalgesia test, cVSDS model mice showed a significantly higher bowel transit rate and increased visceral pain-related behaviors, respectively. These changes persisted for more than a month after the stress session.
In contrast, pathological assessments of histological and inflammatory scores of naïve and cVSDS model mice did not differ. Additionally, keishikashakuyakuto, a clinically used kampo drug for the treatment of IBS, normalized the gut motility change in cVSDS model mice.
Our results indicate that cVSDS model mice exhibit IBS-like symptoms such as chronic intestinal peristaltic changes and abdominal hyperalgesia without organ damage.
We therefore propose the cVSDS paradigm as a novel animal model of IBS with broad validity, elucidating the correlation between depressive states and intestinal abnormalities.
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