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1 Intestinal Disease Research Program, Department of Pathology and Molecular Medicine, and 2 Department of Psychiatry, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
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 
-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.
behavior; corticotropin-releasing hormone; electron microscopy; ion transport; intestinal permeability
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