The DOI matches its Crossref record; 37 of the 38 references it cites were found in a registry or an index.
Neonatal Maternal Separation Causes Colonic Dysfunction in Rat Pups Including Impaired Host Resistance
Abstract
Previous studies have shown that early life stress in the form of intermittent maternal separation (MS) predisposes adult rats to develop stress-induced intestinal mucosal dysfunction and visceral hypersensitivity. However, the mechanism involved in the functional abnormalities is unclear. Our aim was to study immature animals during or shortly after exposure to MS to determine whether there are early pathophysiological changes in the gut. Sprague-Dawley rat pups were individually separated from the dam for 3 h/d from 4 to 21 d of age; nonseparated (NS) control pups remained in the home cage with the dam. On d 19-20, d 24-25, and d 29-30, blood was collected for corticosterone measurement, and colonic tissues were removed for functional and morphologic assessment. Corticosteroid levels were elevated in MS pups compared with NS, indicating that MS was indeed stressful. The distal colon demonstrated significantly enhanced ion secretion and macromolecular permeability at d 19-20 and d 24-25, returning to normal by d 29-30. Electron microscopy and bacterial culture studies indicated bacteria adhering to and penetrating into the colonic epithelium of the MS pups at all time points, while such events were rare in NS pups. The pathophysiological changes were inhibited by injecting pups sc with a corticotropin-releasing hormone (CRH) receptor antagonist daily during MS. Our studies indicate that early psychological trauma predisposes neonatal rats to develop persistent mucosal barrier dysfunction, including impaired host defense to luminal bacteria, by a mechanism involving peripheral CRH receptors.
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“Several studies have demonstrated that neonatal stress can lead to short- and long-term alterations in the diversity and composition of the GM (345–347).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [345]
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“In rodents, neonatal maternal separation is associated with hypothalamic-pituitary-adrenal (HPA) axis alterations, colonic dysfunction and altered intestinal microbiota in neonates, and stress-induced colonic dysfunction and behavioural changes later during adulthood.”
BackgroundSelf-citationBrain–Gut Interactions in Inflammatory Bowel Disease
Bonaz, B. L., & Bernstein, C. N. (2013) · Gastroenterology · doi:10.1053/j.gastro.2012.10.003 · Cited by 667
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Malnutrition as an enteric infectious disease with long-term effects on child development
Guerrant, R. L., Oriá, R. B., Moore, S. R., Oriá, M. O. B., & Lima, A. Â. M. (2008) · Nutrition Reviews · doi:10.1111/j.1753-4887.2008.00082.x · Cited by 556
Microbiota and host determinants of behavioural phenotype in maternally separated mice
De Palma, G., Blennerhassett, P., Lu, J., Deng, Y., Park, A. J., Green, W., Denou, E., Silva, M. A., Santacruz, A., Sanz, Y., et al. (2015) · Nature Communications · doi:10.1038/ncomms8735 · Cited by 517
Metadata
- Authors
- Gareau, M. G., Jury, J., Yang, P. C., MacQueen, G., & Perdue, M. H.
- Affiliations
- McMaster University (CA)
- Corresponding author
- Gareau, Mélanie G
- Venue
- Pediatric Research
- Published
- 2006-01
- Volume
- 59
- Issue
- 1
- Pages
- 83-88
- ISSN
- 0031-3998 (ISSN-L)
- 1530-0447
- OpenAlex
- W1970620887
- Cited by
- 139
- References
- 38
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 8 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 8 · 2017: 4 · 2016: 7 · 2015: 14 · 2014: 13 · 2013: 9 · 2012: 9
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- Crohn's and Colitis Foundation
- Crohn's and Colitis Foundation of Canada
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Health and Development
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- maternal separation, early life stress, neonatal rats, corticosterone, macromolecule permeability, corticotropin-releasing factor receptor, CRH receptor antagonist, visceral hypersensitivity, host resistance
- MeSH terms
- Animals, Animals, Newborn, Bacterial Adhesion, Body Weight, Colon, Colonic Diseases, Corticosterone, Female, Intestinal Mucosa, Maternal Deprivation, Rats, Sprague-Dawley, Receptors, Corticotropin-Releasing Hormone, Rats
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