Stressor-Induced Increases in Circulating, but Not Colonic, Cytokines Are Related to Anxiety-like Behavior and Hippocampal Inflammation in a Murine Colitis Model.

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 , , and in the colonic tissue, but increased , , , and in the MLNs. A network analysis indicated that reductions in colonic were related to elevated MLN and . These inflammatory markers were related to serum and hippocampal IL-17A and associated with anxiety-like behavior. Our data suggest that may protect against extra-colonic inflammation, and when suppressed during stress it is associated with elevated MLN , which may coordinate gut-to-brain inflammation. Our data point to hippocampal as a key correlate of anxiety-like behavior.