Neuronal dysfunction in the amygdala is involved in anxiety-like behaviors accompanying ulcerative colitis

Ulcerative colitis (UC) is a refractory inflammatory bowel disease that causes high rates of psychiatric disorders, such as anxiety and depression. In fact, dextran sodium sulfate (DSS)-treated mice, which are commonly used as a model for UC, exhibit depression- and anxiety-like behaviors. However, the pathogeneses of these psychiatric disorders remain unclear. Acute stress increases immediate-early gene (IEG), including c-fos, expression in the various brain regions. To examine changes in neural activity during acute mild stress exposure in DSS-treated mice, we quantified c-Fos expression after behavioral tests. In the study, samples were collected 1 h after the behavioral test in the stress group, while samples were collected without behavioral tests in the control group. Treatment with 2 % DSS for 7 days induced UC-like symptoms and anxiety-like behaviors in the hole-board and elevated plus-maze tests. Furthermore, the c-Fos expression levels in the prefrontal cortex were significantly elevated in DSS-treated mice in the stress group compared to in those in the control group. Compared to water-treated mice, DSS-treated mice, both with and without stress exposure, showed significantly decreased c-Fos expression level and GluN1 phosphorylation in the amygdala. We found a correlation between DSS-induced anxiety-like behaviors and c-Fos expression in the amygdala. The elevated ERK1/2 phosphorylation levels in the amygdala observed in the water-treated mice exposed to mild acute stress were not exhibited in DSS-treated mice. Moreover, DSS-treated mice showed decreased synaptophysin expression in the amygdala. The neuronal dysfunction in the amygdala may be associated with the onset of anxiety related to UC.