Psychological Stress Induces an Increase in Cholinergic Enteric Neuromuscular Pathways Mediated by Glucocorticoid Receptors

Abstract

Repeated acute stress (RASt) is known to be associated with gastrointestinal dysfunctions. However, mechanisms underlying these effects are not fully understood. While glucocorticoids are clearly identified as hormones of stress, their implication, and those of their specific glucocorticoid receptors (GR), in RASt induced gut dysfunctions remain unclear. The aim of our study was to evaluate the involvement of GR on RASt induced changes in gut motility, particularly through the enteric nervous system (ENS). Using a murine water avoidance stress model, we characterized the impact of RASt upon ENS phenotype and colonic motility. Next, the expression of GR onto the ENS and their functional impact upon RASt induced changes in ENS phenotype and motor response were evaluated. We showed that the GR was expressed in myenteric neurons in the distal colon under basal condition, and that RASt enhanced its nuclear translocation. RASt increased the proportion of ChAT-IR neurons, acetylcholine tissue concentration, and enhanced cholinergic neuromuscular transmission as compared to control. Finally, we showed that GR specific antagonist (CORT108297) prevented the increase of acetylcholine and in vivo colonic motility. Altogether our study suggests that RASt-induced functional changes in motility are, at least partly, due to GR dependent enhanced cholinergic ENS phenotype.