Chronic psychosocial stress induces reversible mitochondrial damage and corticotropin-releasing factor receptor type-1 upregulation in the rat intestine and IBS-like gut dysfunction
Abstract
The association between psychological and environmental stress with functional gastrointestinal disorders, especially irritable bowel syndrome (IBS), is well established. However, the underlying pathogenic mechanisms remain unknown. We aimed to probe chronic psychosocial stress as a primary inducer of intestinal dysfunction and investigate corticotropin-releasing factor (CRF) signaling and mitochondrial damage as key contributors to the stress-mediated effects. Wistar-Kyoto rats were submitted to crowding stress (CS; 8 rats/cage) or sham-crowding stress (SC; 2 rats/cage) for up to 15 consecutive days. Hypothalamic-pituitary-adrenal (HPA) axis activity was evaluated. Intestinal tissues were obtained 1h, 1, 7, or 30 days after stress exposure, to assess neutrophil infiltration, epithelial ion transport, mitochondrial function, and CRF receptors expression. Colonic response to CRF (10 μg/kg i.p.) and hyperalgesia were evaluated after ending stress exposure. Chronic psychosocial stress activated HPA axis and induced reversible intestinal mucosal inflammation. Epithelial permeability and conductance were increased in CS rats, effect that lasted for up to 7 days after stress cessation. Visceral hypersensitivity persisted for up to 30 days post stress. Abnormal colonic response to exogenous CRF lasted for up to 7 days after stress. Mitochondrial activity was disturbed throughout the intestine, although mitochondrial response to CRF was preserved. Colonic expression of CRF receptor type-1 was increased in CS rats, and negatively correlated with body weight gain. In conclusion, chronic psychosocial stress triggers reversible inflammation, persistent epithelial dysfunction, and colonic hyperalgesia. These findings support crowding stress as a suitable animal model to unravel the complex pathophysiology underlying to common human intestinal stress-related disorders, such as IBS.
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Rats exposed to chronic stress exhibited activation of the HPA axis, intestinal mucosal inflammation, increased epithelial permeability, and colonic hyperalgesia.
“For example, rats exposed to chronic stress exhibited activation of the hypothalamic-pituitary-adrenal (HPA) axis, intestinal mucosal inflammation, increased epithelial permeability, and colonic hyperalgesia (183).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [183]
Stress-induced intestinal microbial changes are associated with altered immune response and increased susceptibility to an enteric pathogen in animal studies.
“and the recent animal studies showing that stress-induced intestinal microbial changes are associated with altered immune response (6) and increased susceptibility to an enteric pathogen (183).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [183]
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- Authors
- Vicario, M., Alonso, C., Guilarte, M., Serra, J., Martínez, C., González-Castro, A. M., Lobo, B., Antolín, M., Andreu, A. L., García-Arumí, E., Casellas, M., Saperas, E., Malagelada, J. R., Azpiroz, F., & Santos, J.
- Affiliations
- Universitat Autònoma de Barcelona (ES)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
- Corresponding author
- Santos, Javier
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 37
- Issue
- 1
- Pages
- 65-77
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W2034645377
- Cited by
- 92
- References
- 84
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 5 · 2023: 7 · 2022: 7 · 2021: 4 · 2020: 8 · 2019: 7 · 2018: 6 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 6 · 2013: 5 · 2012: 6
- FWCI
- 5.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- chronic psychosocial stress, crowding stress, irritable bowel syndrome, mitochondrial damage, intestinal mucosal inflammation, epithelial permeability, epithelial ion transport, visceral hypersensitivity, hypothalamic-pituitary-adrenal axis
- MeSH terms
- CRF Receptor, Type 1, Animals, Body Weight, Colon, Corticosterone, Corticotropin-Releasing Hormone, Crowding, Defecation, Disease Models, Animal, Humans, Hyperalgesia, Inflammation, Intestinal Mucosa, Male, Mitochondria, Rats, Inbred WKY, Stress, Psychological, Up-Regulation, Receptors, Corticotropin-Releasing Hormone, Irritable Bowel Syndrome, Rats
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