Experimental Colitis and Visceral Hypersensitivity Are Attenuated by GABA Treatment in Mice

Abstract

Ulcerative colitis (UC) is characterized by a relapsing mucosal inflammation of the large intestine that appears to be due to an overactive response of the colon- immune system provoking rectal bleeding, diarrhea, and abdominal pain. Based on recent data indicating that 1) GABA suppresses immune cell activity, 2) there is a decrease in GABA in the colon associated with the active phase of UC, 3) that restoring GABA tone has beneficial effects such as ameliorating immune and inflammatory response. We aimed to investigate the effects of GABA treatment on colon persistent inflammation following induction of colitis in mice. Persistent inflammation was induced with seven days of dextran sodium sulfate (DSS, 3%) in the drinking water. GABA (40 mg/Kg) was administered orally for the same period as DSS, and the clinical progression of colitis (DAI) was scored each day. A day after the last GABA treatment the visceral sensitivity was assessed with the visceromotor response (VMR) evoked with balloon distention of the colon and then colon samples were collected for measurement of proinflammatory cytokines. Treatment with GABA reduced changes associated with the presence of visceral inflammation including the decrease in colon length, increase in spleen weight, histological damage to the colon mucosa, and the DAI. Furthermore, GABA markedly inhibited the DSS-induced increase in the proinflammatory cytokines TNF-α, IL-12, and IFN-gamma in the colon tissue. Importantly, GABA decreased DSS-induced visceral hypersensitivity. The data suggest that GABA treatment may be an effective therapy for the management of symptoms associated with UC.