title: Altered neurotransmitter expression profile in the ganglionic bowel in Hirschsprung's disease.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Temple Street Children's University Hospital, Dublin 1, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Coyle
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: O'Donnell
authors.affiliation: Temple Street Children's University Hospital, Dublin 1, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: Gillick
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland. Electronic address: prem.puri@ncrc.ie.
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D016022:Case-Control Studies; D003106:Colon / Q000294:innervation / Q000378:metabolism* / Q000601:surgery; D015536:Down-Regulation; D005260:Female; D005455:Fluorescent Antibody Technique; D006627:Hirschsprung Disease / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D007223:Infant; D008297:Male; D018613:Microscopy, Confocal; D018377:Neurotransmitter Agents / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D018377:Neurotransmitter Agents
keywords: Cholinergic; Hirschsprung; Neurotransmitter; Nitric oxide; Pull-through operation