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 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.

• Authors: Johan D Söderholm, Derrick A Yates, Mélanie G Gareau, Ping-Chang Yang, Glenda MacQueen, Mary H Perdue
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 283 Issue 6 Pg. G1257-63 (Dec 2002) ISSN: 0193-1857 [Print] United States
• PMID: 12388189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptide Fragments
• Receptors, Corticotropin-Releasing Hormone
• Corticotropin-Releasing Hormone
• corticotropin releasing hormone (9-41)

Topics

• Animals
• Animals, Newborn (physiology)
• Behavior, Animal
• Biological Transport
• Colonic Diseases (etiology, physiopathology)
• Corticotropin-Releasing Hormone (antagonists & inhibitors, pharmacology)
• Electric Conductivity
• Epithelium (metabolism)
• Female
• Intestinal Mucosa (physiopathology)
• Maternal Deprivation
• Peptide Fragments (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Corticotropin-Releasing Hormone (physiology)
• Stress, Physiological (physiopathology)
• Weight Gain