Repeated predictable stress causes resilience against colitis-induced behavioral changes in mice.

Ahmed M Hassan,Peter Holzer,Rufina Schuligoi,Florian Reichmann,Raphaela Mayerhofer,Piyush Jain,Aitak Farzi

doi:10.3389/fnbeh.2014.00386

Ahmed M Hassan, Peter Holzer + Show 5 more

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https://doi.org/10.3389/fnbeh.2014.00386

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Abstract

Inflammatory bowel disease is associated with an increased risk of mental disorders and can be exacerbated by stress. In this study which was performed with male 10-week old C57Bl/6N mice, we used dextran sulfate sodium (DSS)-induced colitis to evaluate behavioral changes caused by intestinal inflammation, to assess the interaction between repeated psychological stress (water avoidance stress, WAS) and colitis in modifying behavior, and to analyze neurochemical correlates of this interaction. A 7-day treatment with DSS (2% in drinking water) decreased locomotion and enhanced anxiety-like behavior in the open field test and reduced social interaction. Repeated exposure to WAS for 7 days had little influence on behavior but prevented the DSS-induced behavioral disturbances in the open field and SI tests. In contrast, repeated WAS did not modify colon length, colonic myeloperoxidase content and circulating proinflammatory cytokines, parameters used to assess colitis severity. DSS-induced colitis was associated with an increase in circulating neuropeptide Y (NPY), a rise in the hypothalamic expression of cyclooxygenase-2 mRNA and a decrease in the hippocampal expression of NPY mRNA, brain-derived neurotrophic factor mRNA and mineralocorticoid receptor mRNA. Repeated WAS significantly decreased the relative expression of corticotropin-releasing factor mRNA in the hippocampus. The effect of repeated WAS to blunt the DSS-evoked behavioral disturbances was associated with a rise of circulating corticosterone and an increase in the expression of hypothalamic NPY mRNA. These results show that experimental colitis leads to a particular range of behavioral alterations which can be prevented by repeated WAS, a model of predictable chronic stress, while the severity of colitis remains unabated. We conclude that the mechanisms underlying the resilience effect of repeated WAS involves hypothalamic NPY and the hypothalamic-pituitary-adrenal axis.

Highlights

Inflammatory bowel disease (IBD) is a major health problem mainly in the Western countries where the prevalence of IBD is more than 200 per 100,000 inhabitants (Cosnes et al, 2011)
Animals were subjected to a 7-day treatment with dextran sulfate sodium (DSS) (2% in the drinking water) and Water avoidance stress (WAS) (1 h daily), alone or in combination, followed by behavioral testing during days 8–10
Animals were subjected to a 7-day treatment with DSS (2% in the drinking water) and WAS (1 h daily), alone or in combination, and sacrificed for the assay of biochemical factors in the colon, blood and brain on day 8, i.e., 1 day after the end of treatment with DSS and WAS

Summary

Introduction

Inflammatory bowel disease (IBD) is a major health problem mainly in the Western countries where the prevalence of IBD is more than 200 per 100,000 inhabitants (Cosnes et al, 2011). The disease reduces quality of life, and the deterioration of wellbeing is exacerbated in the presence of psychiatric disturbances (Guthrie et al, 2002; Nordin et al, 2002). Several mental disorders including major depression, panic and generalized anxiety are more common in IBD patients than in community controls (Walker et al, 2008; Graff et al, 2009). The relationship between IBD and changes in the brain is emphasized by epidemiological studies showing that stressful life events can be a risk factor for IBD development and relapse (Mawdsley and Rampton, 2006). The continuously accumulating evidence that connects IBD with psychiatric disorders underscores the necessity to study brain reactions to gastrointestinal inflammation

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