Intranasal Oxytocin Administration Ameliorates DSS-induced Abnormal
Stress-related Behavior and Intestinal Inflammation in an IBD Mouse
Model
Abstract
Inflammatory bowel disease (IBD) comprises Crohn’s disease and
ulcerative colitis. In patients with IBD, intestinal inflammation and
psychological comorbidities affect the quality of life. Evidence for the
effectiveness of antipsychotics drugs or psychological therapies in
patients with IBD is currently lacking. However, several studies have
reported that intranasal oxytocin (OT) administration is effective in
individuals with psychological disorders. Therefore, in this study, we
evaluated the effects of intranasal OT on psychological disorders, using
an IBD mouse model established via dextran sodium sulfate (DSS). Our
results showed that intranasal OT improved DSS- induced abnormal
stress-related behavior and restored the DSS-induced alterations in
nNOS/NO, oxytocin receptor (OTR), pERK/ERK and BDNF expression in the
hippocampus. Intranasal OT also ameliorated intestinal inflammation. The
activity of the hypothalamic-pituitary-adrenal axis and the
sympathetic-adrenal medulla axis were also altered by intranasal OT,
without affecting the peripherally-secreted OT. Thus, while intranasal
OT administration increased the concentration of OT in the hypothalamus
compared to that in the untreated IBD mouse, the OT levels in the serum
did not change. Intranasal OT increased the percentages of the M1 and M2
type macrophages and regulatory T (Treg) cells in the IBD mice, in
contrast it decreased the M1/M2 ratio and the percentage of NKp46+NK
cells in the spleen. We found that the protective effects of intranasal
OT administration on impaired stress-coping behavior and intestinal
inflammation could be abolished by splenectomy. In conclusion, the
present study demonstrates that intranasal OT can ameliorate DSS-induced
abnormal stress-related behavior and intestinal inflammation.