Intranasal OT reverted the changes induced by DSS in HPA axis and the sympathetic-adrenal medulla (SAM) axis
Communication between the gut and the brain is largely dependents on different pathways: the HPA axis; neural communication (vagal and sympathetic system); and systemic communication which include peptides (such as OT) and other small molecules31. In the next stage of our study, we investigated the activity of these different pathways. For HPA axis pathway, the enzyme-linked immunosorbent assay (ELISA) analysis demonstrated that the levels of corticotropin-releasing hormone (CRH) were up-regulated in the hypothalamus of the IBD mice in response to DSS-induced inflammation response compared to those in the control mice and that intranasal OT treatment decreased the expression of CRH. Similar results were obtained with adreno-cortico-tropic-hormone (ACTH) and cortisol(Fig.4A-C). Again, these changes were diminished by intranasal atosiban co-treatment(Fig.4A-C). For the systemic communication pathway, we detected the expression of OT in the hypothalamus and OT levels in serum. Endogenous OT is known to play a role in intestinal immunity, and intraperitoneal injection of OT can repair intestinal injury32, While the OT levels in serum increased in the IBD mice, the expression of OT in the hypothalamus did not change (Fig.4D-E). Interestingly, although intranasal OT increased expression of OT in the hypothalamus, the OT levels in serum did not increase following intranasal OT treatment (Fig.4D-E). For the neural communication pathways, we analyzed the catecholamine levels in serum using ELISA to assess the activity of the sympathetic system. The results showed that the catecholamine levels were elevated in IBD mice, and that, in comparison, intranasal OT suppressed catecholamine levels in serum in comparison (Fig.4F). In the vagus nerve system, we decided to focus on the vago-splenic pathway, and in particular, the cholinergic anti-inflammation pathway(CAP)33. Compared with the control group, DSS-induced colitis was associated with a decrease in acetylcholine(ACh)and an increase of TNF-α in the spleen (Fig.4G-H). Intranasal OT treatment reversed the observed decrease in ACh and increase in TNF-α in the spleen of mice with DSS-induced colitis (Fig.4G-H).