Toward a better understanding of the central consequences of intestinal inflammation.

Inflammatory bowel diseases (IBDs), which include Crohn's disease and ulcerative colitis, are inflammatory diseases of the gastrointestinal tract. Quality of life for IBD patients is negatively affected by associated pain and gastrointestinal dysfunction, but also by serious behavioral symptoms that include depression, anxiety, fatigue, and cognitive dysfunction. Because these behavioral comorbidities are poorly understood, we have investigated them in a rat model of IBD caused by infusion of a hapten (trinitrobenzene sulfonic acid (TNBS)) into the lower colon. TNBS colitis has many similarities to Crohn's disease, and we have found that it is associated with changes in central nervous system function. TNBS-treated animals have lowered seizure thresholds, which resolve following remission, and hippocampal slices from such animals display increased excitability. There are significant changes in excitatory, AMPA receptor-mediated transmission, in part due to increased numbers of AMPA receptors lacking the GluR2 subunit. Long-term potentiation and depression are reduced in colitic animals, and the synaptic alterations are reversed if microglial activation and tumor necrosis factor α synthesis within the brain are blocked.