Altered neurotransmitter expression profile in the ganglionic bowel in Hirschsprung's disease.

Abstract

PURPOSE:

Despite having optimal pull-through (PT) surgery for Hirschsprung's disease (HSCR), many patients experience persistent bowel symptoms with no mechanical/histopathological cause. Murine models of HSCR suggest that expression of key neurotransmitters is unbalanced proximal to the aganglionic colonic segment. We aimed to investigate expression of key enteric neurotransmitters in the colon of children with HSCR.

METHODS:

Full-length PT specimens were collected fresh from children with HSCR (n=10). Control specimens were collected at colostomy closure from children with anorectal malformation (n=8). The distributions of neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), and substance P (SP) were evaluated using immunofluorescence and confocal microscopy. Neurotransmitter quantification was with Western blot analysis.

RESULTS:

ChAT expression was high in aganglionic bowel and transition zone but reduced in ganglionic bowel in HSCR relative to controls. Conversely, nNOS expression was markedly reduced in aganglionic bowel but high in ganglionic bowel in HSCR relative to controls. VIP expression was similar in ganglionic HSCR and control colon. SP expression was similar in all tissue types.

CONCLUSION:

Imbalance of key excitatory and inhibitory neurotransmitters in the ganglionic bowel in HSCR may explain the basis of bowel dysmotility after an optimal pull-through operation in some patients.

• Authors: David Coyle, Anne Marie O'Donnell, John Gillick, Prem Puri
• Journal: Journal of pediatric surgery (J Pediatr Surg) Vol. 51 Issue 5 Pg. 762-9 (May 2016) ISSN: 1531-5037 [Electronic] United States
• PMID: 26951962 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Neurotransmitter Agents

Topics

• Biomarkers (metabolism)
• Blotting, Western
• Case-Control Studies
• Colon (innervation, metabolism, surgery)
• Down-Regulation
• Female
• Fluorescent Antibody Technique
• Hirschsprung Disease (metabolism, surgery)
• Humans
• Infant
• Male
• Microscopy, Confocal
• Neurotransmitter Agents (metabolism)
• Up-Regulation