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Abstract

Stress may be a contributing factor in intestinal inflammatory disease; however, the underlying mechanisms have not been elucidated. We previously reported that acute stress altered jejunal epithelial physiology. In this study, we examined both physical and psychological stress-induced functional changes in colonic mucosa. Colonic mucosal tissue from rats subjected to either 2 hr of cold-restraint stress or 1 hr of water-avoidance stress demonstrated altered ionic transport as well as significantly elevated baseline conductance (ionic permeability) and flux of horseradish peroxidase (macromolecular permeability). Intraperitoneal pretreatment with the corticotropin-releasing hormone (CRH) antagonist, a helical CRH(9-41), inhibited the stress-induced abnormalities, while exogenous intraperitoneal administration of CRH, to control rats, mimicked the stress responses and in vitro CRH increased the macromolecular permeability. These results suggest that peripheral CRH mediates stress-induced colonic pathophysiology. We speculate that a stress-induced barrier defect may allow uptake of immunogenic substances into the colonic mucosa, initiating or exacerbating intestinal inflammation.

Pathophysiological Mechanisms of Stress-Induced Intestina Damage

“…Corticotropin-releasing factor (CRF) (also known as corticotropin-releasing hormone) was characterized as the primary hypothalamic peptide responsible for the pituitary-adrenal activation during stress; further studies substantiated the importance of CRF receptors located in the brain to mediate not only the endocrine but also the behavioral, autonomic and visceral responses associated with stress [26][27][28]. Moreover, the recent discovery of novel CRF-related peptides, urocortin 1, urocortin 2 and urocortin 3 as well as CRF receptors in the periphery provide novel insights into the possible significance of the peripheral CRF system in adaptation to stress [29][30][31][32].…”

“…Standard animal models using physical stressors (for example, restraint stress, cold stress, swimming stress, etc) have been developed and characterized [31,35,36]. Psychological stressors applied in either acute or chronic fashion, and maternal separation in neonatal rodents have been the main focus of the studies performed in my laboratory, where the short and long-term effects on intestinal barrier function were characterized [31,[37][38][39][40].…”

“…Psychological stressors applied in either acute or chronic fashion, and maternal separation in neonatal rodents have been the main focus of the studies performed in my laboratory, where the short and long-term effects on intestinal barrier function were characterized [31,[37][38][39][40]. The main psychological stress model we have employed is water avoidance stress (WAS), which induces anxiety (fear of water) in rodents by placing them on a small platform surrounded by shallow water.…”

“…This was demonstrated by increased paracellular permeability assessed by elevated tissue conductance and transport of small molecular probes ( 3 H-mannitol and 51 Cr-EDTA) in the absence of ultra-structural damage of the small intestine [36]. Follow-up studies in rats exposed to a single 1-hour session of WAS found that this psychological stressor was sufficient to cause an increase in both paracellular (by conductance) [36] and transcellular (by HRP flux) permeability [35] in the small [35] and large intestine [31]. HRP was also visualized by electron microscopy in endosomes and within the paracellular spaces in tissue samples from stressed rats but not controls [31].…”

The Effects of Physical and Psychological Stress on the Gastrointestinal Tract: Lessons from Animal Models

“…It is suggested that the repetitive application of the procedure reflects the pattern of daily stress experienced by humans [53]. The procedure consists placing the animal on a glass platform in the middle of a plastic container filled with water; applied for 5 to 10 consecutive days to rats it has demonstrated to activate HPA axis, to induce a reduction in food intake and weight lost, as well as to lead several pathophysiological changes in the gut such as increased intestinal ion secretion [53], increased small bowel [53] and colonic [54,55] permeability, hyperplasia and activation of gastrointestinal mucosal mast cells [54], and even colonic microscopic inflammation [56].…”