Neonatal maternal separation predisposes adult rats to colonic barrier dysfunction in response to mild stress.
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 alpha-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.
Söderholm
Johan D
JD
Intestinal Disease Research Program, Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
Yates
Derrick A
DA
Gareau
Mélanie G
MG
Yang
Ping-Chang
PC
MacQueen
Glenda
G
Perdue
Mary H
MH
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001522:Behavior, Animal; D001692:Biological Transport; D003108:Colonic Diseases / Q000209:etiology* / Q000503:physiopathology; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004553:Electric Conductivity; D004848:Epithelium / Q000378:metabolism; D005260:Female; D007413:Intestinal Mucosa / Q000503:physiopathology*; D008426:Maternal Deprivation; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000502:physiology; D013312:Stress, Physiological / Q000503:physiopathology*; D015430:Weight Gain
D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41)