Psychological stress induces an increase in cholinergic enteric neuromuscular pathways mediated by glucocorticoid receptors

Front Neurosci. 2023 Feb 14:17:1100473. doi: 10.3389/fnins.2023.1100473. eCollection 2023.


Introduction: Repeated acute stress (RASt) is known to be associated with gastrointestinal dysfunctions. However, the mechanisms underlying these effects have not yet been fully understood. While glucocorticoids are clearly identified as stress hormones, their involvement in RASt-induced gut dysfunctions remains unclear, as does the function of glucocorticoid receptors (GR). 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).

Methods: Using a murine water avoidance stress (WAS) model, we characterized the impact of RASt upon the ENS phenotype and colonic motility. We then evaluated the expression of glucocorticoid receptors in the ENS and their functional impact upon RASt-induced changes in ENS phenotype and motor response.

Results: We showed that GR were expressed in myenteric neurons in the distal colon under basal conditions, and that RASt enhanced their nuclear translocation. RASt increased the proportion of ChAT-immunoreactive neurons, the tissue concentration of acetylcholine and enhanced cholinergic neuromuscular transmission as compared to controls. Finally, we showed that a GR-specific antagonist (CORT108297) prevented the increase of acetylcholine colonic tissue level and in vivo colonic motility.

Discussion: Our study suggests that RASt-induced functional changes in motility are, at least partly, due to a GR-dependent enhanced cholinergic component in the ENS.

Keywords: acetylcholine; enteric nervous system; glucocorticoid receptor; motility; stress.

Grants and funding

This work was funded in part by the French non-profit patient association “Adrenals” ( JB was funded in part by a grant “Année Recherche” of the University Hospital of Nantes.