Effect of stress on the paracellular barrier in the rat ileum

Abstract

Background: Restraint stress induces permeability changes in the rat small intestine but little is known of the ultrastructural events leading to defects of the paracellular sealing or of the short term evolution of these alterations. Methods: In the present study, we performed transmission electron microscopy in the terminal ileum perfused with lanthanum after two hours of immobilisation stress and in non-stressed control rats. Moreover, immunohistochemistry of the tight junction (TJ) associated proteins, occludin and zonula occludens 1 (ZO-1), was carried out together with western blot analysis of the transmembrane protein occludin. TJ morphology was also assessed after a 22 hour recovery period. Results: Immobilisation stress induced a significant increase in epithelial permeability to the lanthanum tracer (p<0.005) which recovered completely after 22 hours. Compared with unstressed controls, in stressed rats no differences were found on freeze fracture analysis. The TJ related immunofluorescence signals of occludin and of ZO-1 were irregularly distributed in stressed rats after two hours but returned to a normal pattern at 24 hours although with minor intensity. No quantitative alterations in occludin were detectable in stressed rats by immunoblot whereas a perinuclear concentration of occludin was observed by immunolocalisation. Conclusions: Immobilisation stress induced an increase in TJ permeability in the rat terminal ileum. These changes were mainly due to modifications and redistribution of the TJ transmembrane protein occludin and of the plaque protein ZO-1 whereas protein synthesis, at least that of occludin, was not affected by stress.

Stress Impairs Murine Intestinal Barrier Function: Improvement by Glucagon-Like Peptide-2

“…Clinical and experimental studies have documented significant gut pathophysiology in response to acute and chronic psychological stress. In particular, stressinduced changes described in rats include increased secretory state, altered colonic motility, increased epithelial permeability to small and large probes, damaged mitochondria in epithelial cells, altered epithelial/bacterial interactions, and increased inflammatory infiltrate (Saunders et al, 1997(Saunders et al, , 2002Kiliaan et al, 1998;Santos et al, 2000;Mazzon et al, 2002;Soderholm et al, 2002). Together, the evidence suggests that intestinal dysfunction and inflammation can be initiated by psychological stress in a naïve host (Soderholm et al, 2002).…”

Role of TNF-α in ileum tight junction alteration in mouse model of restraint stress

“…As a result of the stress-induced permeability changes, the same authors also demonstrated enhanced intercellular uptake of macromolecules (29), hypothesizing that this mechanism may contribute to the clinically described flare-ups in patients with inflammatory bowel disease after stressful events. In a recent study Mazzon and colleagues (38) have demonstrated that immobilization stress induced an increase in tight junction (TJ) permeability in the rat terminal ileum. These changes were mainly due to modifications and redistribution of the TJ transmembrane protein occludin and of the plaque protein zonula occludens (ZO)-1 whereas protein synthesis, at least that of occludin, was not affected by stress (38).…”

“…In a recent study Mazzon and colleagues (38) have demonstrated that immobilization stress induced an increase in tight junction (TJ) permeability in the rat terminal ileum. These changes were mainly due to modifications and redistribution of the TJ transmembrane protein occludin and of the plaque protein zonula occludens (ZO)-1 whereas protein synthesis, at least that of occludin, was not affected by stress (38).…”

Glucocorticoids and the Intestinal Environment

“…Acute immobilization stress also induced an increase in TJ permeability in the rat terminal ileum. These changes were mainly due to irregularly distribution of TJ transmembrane protein occludin and of the plaque protein ZO-1 which were seen after 2 hours from the stress induction and returned to a normal pattern within 24 hours [70]. Mazzon and Cuzzocrea [75] also suggested that TNF-has active roles in the increase of tight junction permeability during acute restraint stress.…”

“…The breakdown of tight junctions during bacterial infections results in gut barrier failure, often termed "leaky gut" [20,23]. Proteins that constitute the TJ complex include transmembrane proteins such as occludin, claudin, junction adhesion molecules and intracytoplasmic proteins zonula occludens 1 and 2 (ZO1-ZO2) and members of the membrane-associated guanylate kinase (MAGUK) protein family [70]. Tight junctions are highly dynamic structures, and their permeability is regulated by several physiological and pathophysiological conditions.…”