Neonatal maternal separation predisposes adult rats to colonic barrier dysfunction in response to mild stress
Abstract
Intestinal dysfunction is related to stress and early life events, but the mechanisms are largely unknown. Our aim was to determine whether early trauma predisposes adult rats to intestinal mucosal dysfunction in response to stress. Neonatal Sprague-Dawley rats were individually separated from their mothers for 3 h/day at 4–21 days of age. Between days 80 and 90, separated and control rats were subjected to mild acute stress (30-min water avoidance) or sham stress. Mucosal barrier function and ion transport were assessed in colonic tissues mounted in Ussing chambers. Mild stress increased short-circuit current, conductance, and transepithelial transport of macromolecules in separated rats, while having minimal effects in controls. Pretreatment of the separated rats with a corticotropin-releasing hormone (CRH) antagonist, the peptide α-helical CRH(9–41) injected intraperitoneally 20 min before stress, abolished the stress-induced mucosal changes. Our results indicate that neonatal trauma can induce phenotypic changes in adulthood, including enhanced vulnerability of the gut mucosa to stress via mechanisms involving peripherally located CRH receptors.
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Stressful stimuli can enhance the permeability of the intestinal epithelium, which allows bacterial antigens to penetrate the gut epithelium and triggers an immune response in the intestinal mucosa.
“For example, several studies have demonstrated that stressful stimuli can enhance the permeability of the intestinal epithelium, which allows bacterial antigens to penetrate the gut epithelium and triggers an immune response in the intestinal mucosa.23-27”
From Principles and clinical implications of the brain-gut-enteric microbiota axis (2009) · cites this paper as [26]
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- Authors
- Söderholm, J. D., Yates, D. A., Gareau, M. G., Yang, P.-C., MacQueen, G., & Perdue, M. H.
- Affiliations
- Intestinal Disease Research Program, Department of Pathology and Molecular Medicine, and
- McMaster University (CA)
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2002-12-01
- Volume
- 283
- Issue
- 6
- Pages
- G1257-G1263
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2113258076
- Cited by
- 243
- References
- 37
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 6 · 2023: 9 · 2022: 9 · 2021: 15 · 2020: 9 · 2019: 7 · 2018: 15 · 2017: 6 · 2016: 14 · 2015: 14 · 2014: 18 · 2013: 7 · 2012: 11
- FWCI
- 5.81
- 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 › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Keywords
- neonatal maternal separation, intestinal barrier, water avoidance stress, corticotropin-releasing factor, CRH receptors, short-circuit current, transepithelial transport, early trauma, stress vulnerability
- MeSH terms
- Animals, Animals, Newborn, Behavior, Animal, Biological Transport, Colonic Diseases, Corticotropin-Releasing Hormone, Electric Conductivity, Epithelium, Female, Intestinal Mucosa, Maternal Deprivation, Peptide Fragments, Stress, Physiological, Weight Gain, Rats, Sprague-Dawley, Receptors, Corticotropin-Releasing Hormone, Rats
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