AffiliationNational Children's Research Centre, Our Lady's Children's Hospital, Crumlin,, Dublin 12, Ireland.
MeSHDigestive System Abnormalities/*physiopathology
Enteric Nervous System/abnormalities
MetadataShow full item record
CitationPediatr Surg Int. 2011 May;27(5):491-3.
JournalPediatric surgery international
AbstractPURPOSE: The enteric nervous system (ENS) is a network of neurons and glia that lies within the gut wall. It is responsible for the normal regulation of gut motility and secretory activities. Hirschsprung's disease (HD) is a congenital defect of the ENS, characterised by an absence of ganglia in the distal colon. Intestinal neuronal dysplasia (IND) is a condition that clinically resembles HD, characterised by hyperganglionosis, giant and ectopic ganglia, resulting in intestinal dysmotility. Intestinal ganglioneuromatosis is characterised by hyperplasia and hypertrophy of enteric neuronal cells and causes chronic intestinal pseudo-obstruction (CIPO). Phosphatase and tensin homolog deleted on chromosome 10 (Pten) is a phosphatase that is critical for controlling cell growth, proliferation and cell death. A recent study of Pten knockout mice showed evidence of ganglioneuromatosis in the ENS suggesting a role for this protein in ENS development. Ganglioneuromatosis patients have also been shown to have a decreased level of Pten expression in the colon. The aim of our study was to investigate Pten expression in the ENS of HD and IND patients compared to normal controls. METHODS: Resected tissue from 10 HD and 10 IND type B patients was fixed and embedded in paraffin wax. Normal control colon tissue was obtained from ten patients who underwent a colostomy closure for imperforate anus. Sections were cut and immunohistochemistry was carried out using a Pten antibody. Results were analysed by light microscopy. RESULTS: Staining showed that Pten was strongly expressed in ganglia of both the submucosal and myenteric plexus of normal and HD specimens from the ganglionic colon. Pten expression was significantly reduced in the giant ganglia in IND patients in both the myenteric and submucosal plexuses compared to the normal controls. Specimens from the aganglionic region of HD did not show Pten expression. CONCLUSION: To the best of our knowledge, this is the first study demonstrating a marked reduction of Pten expression in the myenteric and submucous plexuses of IND patients. Neuronal Pten deficiency in IND may disrupt the chemical pathway associated with the proliferation and development of neuronal cells forming mature ganglia and thus cause motility dysfunction.
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- Issue date: 2009 Dec
- Updated results on intestinal neuronal dysplasia (IND B).
- Authors: Meier-Ruge WA, Ammann K, Bruder E, Holschneider AM, Schärli AF, Schmittenbecher PP, Stoss F
- Issue date: 2004 Dec
- Colonic dysmotility in postsurgical patients with Hirschsprung's disease. Potential significance of abnormalities in the interstitial cells of Cajal and the enteric nervous system.
- Authors: Bettolli M, De Carli C, Jolin-Dahel K, Bailey K, Khan HF, Sweeney B, Krantis A, Staines WA, Rubin S
- Issue date: 2008 Aug
- Altered expression of retinoblastoma 1 in Hirschsprung's disease.
- Authors: O'Donnell AM, Coyle D, Puri P
- Issue date: 2016 Nov
- Mast cells and gut nerve development: implications for Hirschsprung's disease and intestinal neuronal dysplasia.
- Authors: Kobayashi H, Yamataka A, Fujimoto T, Lane GJ, Miyano T
- Issue date: 1999 Apr