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).