Enteric nervous system and developmental abnormalities in childhood

Paran, Thambipillai Sri; Rolle, Udo; Puri, Prem

doi:10.1007/s00383-006-1782-9

Cited by 14 publications

(6 citation statements)

References 170 publications

(181 reference statements)

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“…During the last years, several studies have been performed demonstrating the feasibility of isolation and transplantation of neural crest derived stem cells [18,23,[52][53][54][55][56]. Based on the heterogenous genetic background and previous investigations concerning the etiology of the disease, where abnormal micoroenvironment or a secondary cell death after colonization led to aganglionosis [24,25,29,30,[57][58][59][60], it must be discussed whether the individual microenvironment allows a successful and longstanding transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations of the tyrosine kinase RET, the common signaling receptor of all GDNF related ligands, account for 50% of familial HSCR [30]. A lack of GDNF itself leads to the complete absence of enteric neurons in mice [31,32], while its role in HSCR is not clear up to now [30,33,34].…”

Section: Introductionmentioning

confidence: 99%

“…Even if the exact etiology is still unknown, evidence from animal models and human genetic studies point to RET as one of the major genes involved in HSCR pathogenesis [35][36][37][38]. Mutations of the tyrosine kinase RET, the common signaling receptor of all GDNF related ligands, account for 50% of familial HSCR [30]. A lack of GDNF itself leads to the complete absence of enteric neurons in mice [31,32], while its role in HSCR is not clear up to now [30,33,34].…”

Section: Introductionmentioning

confidence: 99%

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The microenvironment in the Hirschsprung's disease gut supports myenteric plexus growth

Hagl

Rauch²,

Klotz³

et al. 2012

Int J Colorectal Dis

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The amount of the factors varied considerably between the individual segments and also from patient to patient. Four major expression patterns could be detected. While all extracts tested lead to a significant increase in neurite outgrowth compared to the control, extracts from proximal segments tended to have more prominent effects. In one experiment, extracts from all individual segments of a single patient were tested. Neurite outgrowth, neuronal survival, and branching pattern varied from segment to segment, but all HSCR-muscle-protein extracts increased neuronal survival and network formation. Smooth muscle protein from aganglionic bowel supports the survival and outgrowth of myenteric neurons and NCSCs and is so an appropriate target for neural stem cell treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The microenvironment in the Hirschsprung's disease gut supports myenteric plexus growth

Hagl

Rauch²,

Klotz³

et al. 2012

Int J Colorectal Dis

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“…The MMC is rarely observed in the preterm infant and although it occurs in the term infant, it is still immature, 7,8 compared with the adult, as is propulsion of nutrients after feeding 1,7 . It is noteworthy that the development of human ENS continues after birth through the first years of life 9–11 . To date, there is a relatively consistent amount of information on the neurochemistry of the human adult ENS but very few data are available in the child 12 .…”

Section: Introductionmentioning

confidence: 99%

Tonic inhibition of human small intestinal motility by nitric oxide in children but not in adults

Wittmeyer

Merrot

Mazet

2010

Neurogastroenterology &Amp; Motility

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Background Gastrointestinal motility is dependent on neural influences that largely involve the enteric nervous system (ENS). The main motor patterns that occur in the fasted and fed state are noticeably different in children compared with adults. Although the development of the ENS continues after birth, there is no data on the contractile activity of segments of small intestine from young children. This study was designed to provide data on the development of muscle control by the human ENS with particular attention to acetylcholine (ACh) and nitric oxide (NO) as the primary neurotransmitters of enteric motor neurons, respectively. Methods Small intestinal specimens were obtained from 11 children and six adults undergoing surgery for various diseases. The mechanical activity of the circular muscle was recorded in vitro. The effects of N x -nitro-L-arginine methyl ester hydrochloride, an inhibitor of NO synthesis, and of atropine, an antagonist of muscarinic receptors, were tested on the spontaneous motility and responses to nerve stimulation. Key Results Spontaneous motility was observed in all preparations. Responses to nerve stimulation were identical in child and adult. No tonic cholinergic excitation of small intestinal motility was observed either in child or in adult. Inhibition of NO synthesis induced a major disinhibition of motility in child but not in adult. Conclusions & Inferences Spontaneous intestinal motility and cholinergic and nitrergic neurotransmission are present from birth. NO provides a tonic inhibition of intestinal motility only in child. Our study indicates that NO may be a major player in shaping the ontogenic development of intestinal motility in human.

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“…There are only a few reports in the literature about maturation of the enteric nervous system (ENS) in the normoganglionic (Ng) segment of bowel from cases of Hirschsprung's disease (HD) [1,2]. We hypothesized that in HD (including long segment HD) as well as total colonic aganglionosis (TCA), developmental maturation of the ENS in the Ng segment may also be compromised, since even after Ng segment pull-through (PT) there is a subgroup of HD patients [3] whose post-operative outcome is unsatisfactory and some HD patients who tend to have diarrhea/enterocolitis [3].…”

Section: Introductionmentioning

confidence: 99%

Developmental anomalies of the enteric nervous system in normoganglionic segments of bowel from rats with total colonic aganglionosis

et al. 2007

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Polysialyated neural cell adhesion molecule (PSA-NCAM) is a marker for immature neurons and S100 beta is a known marker for enteric glia. The aim of this study was to determine the maturation of the enteric nervous system (ENS) in normoganglionic (Ng) bowel from rats with total colonic aganglionosis (TCA). Ng ileum was obtained from TCA rats (spotting lethal: mutant, sl/sl: n = 15) at 10, 19, and 24 days of age (n = 5 for each age). Normal control Ng ileum was obtained from wild type littermates (+/+, n = 25) at 10, 19, 24, 30, and 60 days of age (n = 5 for each age). Specimens were studied with immunohistochemistry for PSA-NCAM and S100 beta. On H-E staining, normal mature ganglion cells (GC) were identified in submucus and myenteric plexuses in all specimens from TCA rats and normal controls. For PSA-NCAM, submucus and myenteric GC in control ileum were strongly positive at 10 days old, weakly positive at 19 days old, and did not stain from 24 days old and after. However, in all ileum specimens from TCA rats, both submucus and myenteric GC were strongly positive for PSA-NCAM regardless of age. For S100 beta, submucus and myenteric glial cells in control ileum were negative at 10 and 19 days old, but positive from 24 days old and after. However, in all ileum specimens from TCA rats, submucus and myenteric glial cells were S100 beta negative regardless of age. Our results suggest that GC in the Ng segment of TCA rats remain immature beyond an age when they should be mature.

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Enteric nervous system and developmental abnormalities in childhood

Cited by 14 publications

References 170 publications

The microenvironment in the Hirschsprung's disease gut supports myenteric plexus growth

The microenvironment in the Hirschsprung's disease gut supports myenteric plexus growth

Tonic inhibition of human small intestinal motility by nitric oxide in children but not in adults

Developmental anomalies of the enteric nervous system in normoganglionic segments of bowel from rats with total colonic aganglionosis

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