Chronic peripheral administration of corticotropin-releasing factor causes colonic barrier dysfunction similar to psychological stress
Abstract
Chronic psychological stress causes intestinal barrier dysfunction and impairs host defense mechanisms mediated by corticotrophin-releasing factor (CRF) and mast cells; however, the exact pathways involved are unclear. Here we investigated the effect of chronic CRF administration on colonic permeability and ion transport functions in rats and the role of mast cells in maintaining the abnormalities. CRF was delivered over 12 days via osmotic minipumps implanted subcutaneously in wild-type (+/+) and mast cell-deficient (Ws/Ws) rats. Colonic segments were excised for ex vivo functional studies in Ussing chambers [short-circuit current (Isc), conductance (G), and macromolecular permeability (horseradish peroxidase flux)], and analysis of morphological changes (mast cell numbers and bacterial host-interactions) was determined by light and electron microscopy. Chronic CRF treatment resulted in colonic mucosal dysfunction with increased Isc, G, and horseradish peroxidase flux in+/+but not in Ws/Ws rats. Furthermore, CRF administration caused mast cell hyperplasia and abnormal bacterial attachment and/or penetration into the mucosa only in+/+rats. Finally, selective CRF agonist/antagonist studies revealed that stimulation of CRF-R1 and CRF-R2 receptors induced the elevated secretory state and permeability dysfunction, respectively. Chronic CRF causes colonic barrier dysfunction in rats, which is mediated, at least in part, via mast cells. This information may be useful in designing novel treatment strategies for stress-related gastrointestinal disorders.
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Alterations in gut barrier integrity enable bacteria and microbial products to translocate across the mucosa and epithelium, interfacing with immune and neuronal cells.
“Alterations in gut barrier integrity enable bacteria (and microbial-products) to translocate across the mucosa and epithelium, interfacing with immune and neuronal cells (356, 357).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [357]
Several studies have demonstrated that CRF mediates its effects via mast cell activation.
“Several studies have demonstrated that CRF mediates its effects via mast cell activation [6], [11], [17].”
From CRF induces intestinal epithelial barrier injury via the release of mast cell proteases and TNF-α (2012) · cites this paper as [11]
Chronic administration of CRF increases conductance and decreases TER in rodents.
“Chronic administration of CRF increases conductance and thus decreases in TER in rodents [11] whereas our ex vivo model would represent acute CRF effects.”
From CRF induces intestinal epithelial barrier injury via the release of mast cell proteases and TNF-α (2012) · cites this paper as [11]
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- Authors
- Teitelbaum, A. A., Gareau, M. G., Jury, J., Yang, P. C., & Perdue, M. H.
- Affiliations
- McMaster University (CA)
- University of Toronto (CA)
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2008-09
- Volume
- 295
- Issue
- 3
- Pages
- G452-G459
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2122927576
- Cited by
- 116
- References
- 52
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 3 · 2017: 11 · 2016: 6 · 2015: 6 · 2014: 9 · 2013: 10 · 2012: 8
- FWCI
- 5.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- corticotropin-releasing factor, psychological stress, mast cells, colonic permeability, ion transport, CRF1 receptor, CRF receptor 2, short-circuit current
- MeSH terms
- CRF Receptor, Type 1, Animals, Bacterial Adhesion, Colon, Colonic Diseases, Corticotropin-Releasing Hormone, Disease Models, Animal, Drug Administration Schedule, Electric Conductivity, Hyperplasia, Intestinal Mucosa, Intestinal Secretions, Male, Mast Cells, Permeability, Rats, Inbred Strains, Stress, Psychological, Time Factors, Infusion Pumps, Implantable, Ion Transport, Receptors, Corticotropin-Releasing Hormone, Rats
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