Chronic restraint stress induces gastrointestinal function alternation: A potential role of the ArhGEF18-RhoA/Rho signaling pathway in the brain–gut axis under stress

Depression is one of the common psychiatric diseases worldwide. Previous studies showed that chronic stress could increase defecation and inhibit weight gain; however, the effects of chronic stress on gastrointestinal peristalsis had not been clarified. To study the mechanisms of depression, chronic restraint stress (CRS) is widely used as a traditional depressive animal model. In this study, we investigate the effects of CRS on gastric emptying and intestinal propulsion in mice. Our results showed that the mice exhibited obvious depression-like behaviors 4 weeks after CRS. Compared with the control group, gastric emptying and intestinal propulsion were significantly decreased in the CRS group. Further, we examined the expression of ArhGEF18, a Rho-specific guanine nucleotide exchanging factor, which was significantly reduced in the gut in the CRS group. Therefore, CRS caused depressive behaviors and abnormal gastrointestinal function. The ArhGEF18-RhoA/Rho signaling pathway may be a potential mediator in the brain–gut axis under stress.