Indiscriminate loss of myenteric neurones in the TNBS-inflamed guinea-pig distal colon.

This investigation was conducted to establish whether guinea-pig trinitrobenzene sulfonic acid (TNBS)-colitis was associated with a change in the number of neurones of the myenteric plexus, and, if so, whether select subpopulations of neurones were affected. Total neurones were quantified with human (Hu) antiserum, and subpopulations were evaluated with antisera directed against choline acetyltransferase, nitric oxide synthase, calretinin, neuronal nuclear protein or vasoactive intestinal peptide (VIP). Colitis was associated with a loss of 20% of the myenteric neurones, most of which occurred during the first 12 h past-TNBS administration. During this period, myenteric ganglia were infiltrated with neutrophils while lymphocytes appeared at a later time-point. The neuronal loss persisted at a 56-day time-point, when inflammation had resolved. The decrease in myenteric neurones was not associated with a decrease in any given subpopulation of neurones, but the proportion of VIP-immunoreactive neurones increased 6 days following TNBS administration and returned to the control range at the 56 days. These findings indicate that there is an indiscriminant loss of myenteric neurones that occurs during the onset of TNBS-colitis, and the loss of neurones may be associated with the appearance of neutrophils in the region.

Serotonin transporter function and expression are reduced in mice with TNBS-induced colitis.

Regulated release of serotonin (5-HT) from enterochromaffin (EC) cells activates neural reflexes that are involved in gut motility, secretion, vascular perfusion and sensation. The 5-HT-selective reuptake transporter (SERT) terminates serotonergic signalling in the intestinal mucosa. The aim of this investigation was to determine whether mucosal 5-HT content, release, and/or reuptake are altered in a murine model of immune cell-mediated colitis. Experiments were conducted 6 days after colitis was induced by 2,4,6-trinitrobenzene sulfonic acid, a time point when macroscopic and histological damage scores indicated significant inflammation. During inflammation, SERT transcript levels and immunoreactivity were reduced, and the uptake of [3H] 5-HT was impaired. Increases in mucosal 5-HT content and the number of 5-HT-immunoreactive mast cells in the lamina propria were also detected in the inflamed region, whereas EC cell numbers did not change. Mucosal 5-HT released under basal and stimulated conditions was unchanged in animals with colitis. These data suggest that murine colitis alters 5-HT signalling by increasing 5-HT availability through decreased 5-HT uptake by mucosal epithelial cells. These findings support the concept that altered 5-HT signalling could be a contributing factor in altered gut function and sensitivity in inflammatory bowel disease.