Dextran sulfate sodium-induced colitis alters stress-associated behaviour and neuropeptide gene expression in the amygdala-hippocampus network of mice

Florian Reichmann,Ahmed Mostafa Hassan,Peter Holzer,Piyush Jain,Rufina Schuligoi,Aitak Farzi

doi:10.1038/srep09970

Florian Reichmann, Ahmed Mostafa Hassan + Show 4 more

Open Access

https://doi.org/10.1038/srep09970

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Journal: Scientific Reports	Publication Date: Jun 12, 2015
Citations: 63	License type: CC BY 4.0

Affiliation: Medical University of Graz

Abstract

Psychological stress causes disease exacerbation and relapses in inflammatory bowel disease (IBD) patients. Since studies on stress processing during visceral inflammation are lacking, we investigated the effects of experimental colitis as well as psychological stress on neurochemical and neuroendocrine changes as well as behaviour in mice. Dextran sulfate sodium (DSS)-induced colitis and water avoidance stress (WAS) were used as mouse models of colitis and mild psychological stress, respectively. We measured WAS-associated behaviour, gene expression and proinflammatory cytokine levels within the amygdala, hippocampus and hypothalamus as well as plasma levels of cytokines and corticosterone in male C57BL/6N mice. Animals with DSS-induced colitis presented with prolonged immobility during the WAS session, which was associated with brain region-dependent alterations of neuropeptide Y (NPY), NPY receptor Y1, corticotropin-releasing hormone (CRH), CRH receptor 1, brain-derived neurotrophic factor and glucocorticoid receptor gene expression. Furthermore, the combination of DSS and WAS increased interleukin-6 and growth regulated oncogene-α levels in the brain. Altered gut-brain signalling in the course of DSS-induced colitis is thought to cause the observed distinct gene expression changes in the limbic system and the aberrant molecular and behavioural stress responses. These findings provide new insights into the effects of stress during IBD.

Highlights

Psychological stress causes disease exacerbation and relapses in inflammatory bowel disease (IBD) patients
Stress is a crucial factor in the course of chronic visceral inflammation, which points to a close pathogenic interaction between the brain and gut
Studies on central adaptation processes contributing to disturbances of stress responsiveness, brain function and emotional-affective behaviour during visceral inflammation are largely lacking

Summary

Introduction

Psychological stress causes disease exacerbation and relapses in inflammatory bowel disease (IBD) patients. To evaluate the effects of colitis on the stress response at the functional level, we assessed whether DSS treatment alters behaviour during WAS. DSS-treated mice had higher basal as well as post-stress corticosterone levels (90 min after WAS) than untreated animals (Fig. 2d).

Results

Conclusion