%A Xu,Ying %A Cui,Su-Ying %A Ma,Quan %A Shi,Jing %A Yu,Ying %A Li,Jian-Xin %A Zheng,Liang %A Zhang,Yi %A Si,Jian-Min %A Yu,Ying-Cong %D 2018 %J Frontiers in Pharmacology %C %F %G English %K Irritable Bowel Syndrome,Depression,Anxiety,Trans-resveratrol,Phosphodiesterases 4A %Q %R 10.3389/fphar.2018.00631 %W %L %M %P %7 %8 2018-June-15 %9 Original Research %# %! trans-Resveratrol ameliorates stress-induced irritable bowel syndrome %* %< %T trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like Behaviors by Regulation of Brain-Gut Axis %U https://www.frontiersin.org/articles/10.3389/fphar.2018.00631 %V 9 %0 JOURNAL ARTICLE %@ 1663-9812 %X Background: Irritable bowel syndrome (IBS) is a functional disorder characterized by abdominal pain and abnormalities in defecation associated with psychiatric disorders such as depression and anxiety due to the dysfunction of brain-gut axis. This study aims to determine whether trans-Resveratrol affects chronic-acute combined stress (CACS)-induced IBS-like symptoms including depression, anxiety and intestinal dysfunction.Methods: ICR male mice were exposed to the CACS for 3 weeks. trans-Resveratrol were administrated daily (2.5, 5, and 10 mg/kg, i.g.) 30 min before CACS. Behavioral tests were performed to evaluate the treatment effects of trans-Resveratrol on IBS. Hippocampus tissues were collected and processed Golgi staining and immuno-blot analysis. Ileum and colon tissues were collected and processed Hematoxylin and Eosin staining and immuno-blot analysis.Results: Administration with trans-Resveratrol before CACS for 3 weeks significantly reversed CACS-induced depression- and anxiety-like behaviors and intestinal dysfunction in mice, which implied a crucial role of trans-Resveratrol in treatment of IBS-like disorder. Furthermore, trans-Resveratrol improved hippocampal neuronal remodeling, protected ileal and colonic epithelial barrier structure against CACS insults. The further study suggested that trans-Resveratrol normalized phosphodiesterases 4A (PDE4A) expression and CREB-BDNF signaling that were disturbed by CACS. The increased pCREB and BDNF expression in the hippocampus were found, while decreased pCREB and BDNF levels were observed after treatment with trans-Resveratrol.Conclusions: The dual effects of trans-Resveratrol on stress-induced psychiatric and intestinal dysfunction may be related to normalization of PDE4A expression and subsequent pCREB-BDNF signaling in the hippocampus, ileum and colon.