Abstract
Stressor exposure increases colonic inflammation. Because inflammation leads to anxiety-like behavior, we tested whether stressor exposure in mice recovering from dextran-sulfate-sodium (DSS)-induced colitis enhances anxiety-like behavior. Mice received 2% DSS for five consecutive days prior to being exposed to a social-disruption (SDR) stressor (or being left undisturbed). After stressor exposure, their behavior was tested and colitis was assessed via histopathology and via inflammatory-cytokine measurement in the serum and colon. Cytokine and chemokine mRNA levels in the colon, mesenteric lymph nodes (MLNs), hippocampus, and amygdala were measured with RT-PCR. SDR increased anxiety-like behaviors, which correlated with serum and hippocampal IL-17A. The stressor also reduced IL-1β, CCL2, and iNOS in the colonic tissue, but increased iNOS, IFNγ, IL-17A, and TNFα in the MLNs. A network analysis indicated that reductions in colonic iNOS were related to elevated MLN iNOS and IFNγ. These inflammatory markers were related to serum and hippocampal IL-17A and associated with anxiety-like behavior. Our data suggest that iNOS may protect against extra-colonic inflammation, and when suppressed during stress it is associated with elevated MLN IFNγ, which may coordinate gut-to-brain inflammation. Our data point to hippocampal IL-17A as a key correlate of anxiety-like behavior.
Highlights
We have previously shown that challenging mice with the colonic pathogen Citrobacter rodentium during exposure to either a prolonged-restraint stressor or to a social-disruption stressor significantly increases colonic histopathology and colonic cytokines and immune factors, such as iNOS, TNFα, IFNγ, and REG3γ [11,12]
Inflammatory mediators and cytokines, including iNOS, IFNγ, IL-1β, IL-6, TNFα, IL-17A, and IL-22 were measured in the colon, mesenteric lymph nodes, blood, and brain regions that are associated with behavioral responses to stress in order to determine whether they correlated with stressor-induced increases in colonic inflammation and/or anxiety-like behavior
Behavior was observed to assess anxiety-like behavior in the light/dark-preference test or in the (A) Time spent in the dark was significantly higher in the stress group vs. the control group * p < 0.05
Summary
Others have shown that giving mice DSS to induce colonic inflammation during stressor exposure exacerbates colitis, marked by increases in IL-6, IFNγ, and TNFα and colonic histopathology [17,18] While these previous studies clearly showed that stress during active colitis increases inflammation, they did not assess the behaviors that are often comorbid in patients with IBD. Inflammatory mediators and cytokines, including iNOS, IFNγ, IL-1β, IL-6, TNFα, IL-17A, and IL-22 were measured in the colon, mesenteric lymph nodes, blood, and brain regions that are associated with behavioral responses to stress (i.e., hippocampus and amygdala) in order to determine whether they correlated with stressor-induced increases in colonic inflammation and/or anxiety-like behavior. Stressor Exposure Increases Anxiety-like Behavior in Mice Given DSS despite the Lack of
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
