Neonatal maternal deprivation triggers long term alterations in colonic epithelial barrier and mucosal immunity in rats

Abstract

Background: Stressful events in the early period of life (for example, maternal deprivation) have been shown to modify adult immune and gastrointestinal tract functions. The present study aimed to establish whether maternal deprivation affects colonic epithelial barrier and the development of an experimental colitis in adult rats.

Methods: Male Wistar rat pups were separated during postnatal days 2-14 or left undisturbed with their dam. At 12 weeks of age, we assessed colonic paracellular permeability, bacterial translocation, myeloperoxidase (MPO) activity, mucosal mast cell density, cytokine (interleukin (IL)-1 beta, IL-2, IL-4, IL-10, and interferon gamma (IFN-gamma)) mRNA expression, and macroscopic damage. Total gut permeability, MPO activity, and macroscopic damage were also assessed four days after intracolonic administration of 2,4,6-trinitrobenzenesulphonic acid (TNBS).

Results: Maternal deprivation triggered a significant increase in colonic permeability associated with bacterial translocation into the mesenteric lymph nodes, liver, and spleen. These alterations were associated with some macroscopic damage and an increase in colonic MPO activity, mucosal mast cell density, and cytokine mRNA expression. Intracolonic infusion of TNBS induced a significantly higher inflammatory reaction in separated animals, as judged by enhanced MPO colonic levels, total gut permeability, and macroscopic lesions.

Conclusions: Maternal deprivation promotes long term alterations in the colonic epithelial barrier associated with an exaggerated immune response to an external immune stimulus. This suggests a role for early psychological factors in the regulation of colonic mucosal barrier in later life.

Figure 1

Effect of neonatal stress on total gut (A) and colonic (B) paracellular permeability in 12 week old rats. Values are mean (SEM) (n = 8 in each group). *p<0.05 between deprived and control rats.

Figure 2

Effect of neonatal stress on colonic myeloperoxidase (MPO) activity (A) and mucosal mast cell number (B) in 12 week old rats. Values are mean (SEM) (n = 8 in each group). *p<0.05 between deprived and control rats.

Figure 3

Effect of neonatal stress on 2,4,6-trinitrobenzenesulphonic acid (TNBS) induced colitis. Macroscopic damage score (A), myeloperoxidase (MPO) activity (B), and total gut permeability (C) were assessed in 12 week old rats. These parameters were determined four days after intracolonic administration of TNBS. Values are mean (SEM) (n = 8 in each group). *p<0.05 between deprived and control rats.