The precipitation of behavioral defects due to inflammation in the DSS mouse model of colitis (LB748)

Abstract

Background: Anxiety, depression, and altered memory have been previously associated with intestinal diseases, including inflammatory bowel disease (IBD). Understanding the association between these behavioral changes and IBD may provide clinical significance seeing as concomitant mood disorders often increase a patient’s risk of developing secondary functional gastrointestinal diseases (FGIDs). Aims: The aim of this study was to determine whether active intestinal inflammation precipitates behavioral defects in memory and anxiety and to determine if these changes persist through the resolution of inflammation. Methods: Dextran Sodium Sulfate (DSS) was administered for 5 days via drinking water followed by either 3 days for active inflammation studies or 8 days for resolution of inflammation studies. Mice were weighed daily and colon lengths were measure at the time of sacrifice in order to assess the degree of sickness. Anxiety‐like behavior (light/dark box) and memory (novel object test) were assessed in the DSS mice vs. controls (WT;C57BL/6). Results: DSS mice at the peak of inflammation demonstrated impairments in non‐spatial memory with an exploration ratio of 54.06 +/‐ 1.84 while controls had a mean exploration ratio of 57.91 +/‐ 1.29 (p<.01; n=13). Anxiety‐like behavior was also evident in the DSS mice, which spent 133.91 +/‐10.17 seconds in the light area of the light/dark box while the controls spent 174 +/‐ 14.51 seconds in the light area (p<.04; n=11). These behavioral defects did not persist at the resolution of intestinal inflammation. However, physiological changes, such as a shortening of the colon, were equally evident at the peak of inflammation as well as at the resolution phase. Conclusions: At the peak of inflammation, the DSS mouse model of colitis displays altered baseline behaviors in regards to memory and anxiety. Although physiological changes persist at the resolution of colitis as seen with persistent shortening of the colon, behavioral defects are not evident post inflammation. Taken together, these findings indicate and underlying connection between the brain and the gut relevant to the context of Inflammatory Bowel Disease.