Morphological and functional alterations of the myrenteric plexus in rats with TNBS-induced colitis

The 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced model of experimental colitis was used to investigate the time-course of alterations in enteric neurotransmission and/or smooth muscle function that occur in chronic infla mmation. Myenteric plexus morphology (immunocytochemical markers), function al integrity of cholinergic neurons (H-3-choline uptake, acetylcholine rele ase and contractile response to electrical field stimulation) and smooth mu scle integrity (contractile response to exogenous acetylcholine) were deter mined 2, 7, 15, and 30 days after TNBS treatment. In TNBS-treated rats exte nsive ulcerations of the mucosa and/or the submucosa and increase in coloni c weights were accompanied by significant reduction in H-3-choline uptake, acetylcholine release and contractile response to stimulation of enteric ne rves. These changes were maximal 7 and 15 days after TNBS treatment. Immuno cytochemical marker (PGP 9.5, SNAP 25, synaptophysin and S100 protein) expr ession was absent in necrotic areas of colons removed 7 days post-injury an d partially reduced in colons removed 15 days after TNBS treatment. By cont rast, the contractile response to exogenous acetylcholine was significantly increased after 7 days in both inflamed and uninflamed regions and returne d to control values by day 30. Likewise, an almost complete recovery of neu ral cholinergic function and of myenteric plexus morphology was observed 30 days after TNBS treatment. These data suggest that TNBS-induced colitis is associated with progressive and selective alterations in myenteric plexus structure and function, with consequent reduction of cholinergic neurotrans mission and abnormality in colonic contractility. The reversibility of myen teric plexus disruption is a clear indication of neuronal plasticity within enteric nervous system as an adaptative mechanism against inflammatory cha llenges.