Dataset Information

Prenatal intestinal obstruction affects the myenteric plexus and causes functional bowel impairment in fetal rat experimental model of intestinal atresia.

ABSTRACT:

Background

Intestinal atresia is a rare congenital disorder with an incidence of 3/10,000 birth. About one-third of patients have severe intestinal dysfunction after surgical repair. We examined whether prenatal gastrointestinal obstruction might effect on the myenteric plexus and account for subsequent functional disorders.

Methodology/principal findings

We studied a rat model of surgically induced antenatal atresia, comparing intestinal samples from both sides of the obstruction and with healthy rat pups controls. Whole-mount preparations of the myenteric plexus were stained for choline acetyltransferase (ChAT) and nitric oxide synthase (nNOS). Quantitative reverse transcription PCR was used to analyze mRNAs for inflammatory markers. Functional motility and permeability analyses were performed in vitro. Phenotypic studies were also performed in 8 newborns with intestinal atresia. In the experimental model, the proportion of nNOS-immunoreactive neurons was similar in proximal and distal segments (6.7±4.6% vs 5.6±4.2%, p?=?0.25), but proximal segments contained a higher proportion of ChAT-immunoreactive neurons (13.2±6.2% vs 7.5±4.3%, p?=?0.005). Phenotypic changes were associated with a 100-fold lower concentration-dependent contractile response to carbachol and a 1.6-fold higher EFS-induced contractile response in proximal compared to distal segments. Transcellular (p?=?0.002) but not paracellular permeability was increased. Comparison with controls showed that modifications involved not only proximal but also distal segments. Phenotypic studies in human atresia confirmed the changes in ChAT expression.

Conclusion

Experimental atresia in fetal rat induces differential myenteric plexus phenotypical as well as functional changes (motility and permeability) between the two sides of the obstruction. Delineating these changes might help to identify markers predictive of motility dysfunction and to define guidelines for post-surgical care.

SUBMITTER: Khen-Dunlop N

PROVIDER: S-EPMC3648556 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Prenatal intestinal obstruction affects the myenteric plexus and causes functional bowel impairment in fetal rat experimental model of intestinal atresia.

Khen-Dunlop Naziha N Sarnacki Sabine S Victor Anais A Grosos Celine C Menard Sandrine S Soret Rodolphe R Goudin Nicolas N Pousset Maud M Sauvat Frederique F Revillon Yann Y Cerf-Bensussan Nadine N Neunlist Michel M

PloS one 20130508 5

<h4>Background</h4>Intestinal atresia is a rare congenital disorder with an incidence of 3/10,000 birth. About one-third of patients have severe intestinal dysfunction after surgical repair. We examined whether prenatal gastrointestinal obstruction might effect on the myenteric plexus and account for subsequent functional disorders.<h4>Methodology/principal findings</h4>We studied a rat model of surgically induced antenatal atresia, comparing intestinal samples from both sides of the obstruction ...[more]

PMID: 23667464

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Project description:BACKGROUND: Within the gut the autonomous enteric nervous system (ENS) is able to sense mechanical stimuli and to trigger gut reflex behaviour. We previously proposed a novel sensory circuit in the ENS which consists of multifunctional rapidly adapting mechanosensitive enteric neurons (RAMEN) in the guinea pig. The aim of this study was to validate this concept by studying its applicability to other species or gut regions. METHODOLOGY/PRINCIPAL FINDINGS: We deformed myenteric ganglia in the mouse small and large intestine and recorded spike discharge using voltage sensitive dye imaging. We also analysed expression of markers hitherto proposed to label mouse sensory myenteric neurons in the ileum (NF145kD) or colon (calretinin). RAMEN constituted 22% and 15% of myenteric neurons per ganglion in the ileum and colon, respectively. They encoded dynamic rather than sustained deformation. In the colon, 7% of mechanosensitive neurons fired throughout the sustained deformation, a behaviour typical for slowly adapting echanosensitive neurons (SAMEN). RAMEN and SAMEN responded directly to mechanical deformation as their response remained unchanged after synaptic blockade in low Ca(++)/high Mg(++). Activity levels of RAMEN increased with the degree of ganglion deformation. Recruitment of more RAMEN with stronger stimuli may suggest low and high threshold RAMEN. The majority of RAMEN were cholinergic but most lacked expression of NF145kD or calretinin. CONCLUSIONS/SIGNIFICANCE: We showed for the first time that fundamental properties of mechanosensitive enteric neurons, such as firing pattern, encoding of dynamic deformation, cholinergic phenotype and their proportion, are conserved across species and regions. We conclude that RAMEN are important for mechanotransduction in the ENS. They directly encode dynamic changes in force as their firing frequency is proportional to the degree of deformation of the ganglion they reside in. The additional existence of SAMEN in the colon is likely an adaptation to colonic motor patterns which consist of phasic and tonic contractions.

Dataset Information

Prenatal intestinal obstruction affects the myenteric plexus and causes functional bowel impairment in fetal rat experimental model of intestinal atresia.

Background

Methodology/principal findings

Conclusion

Publications

Prenatal intestinal obstruction affects the myenteric plexus and causes functional bowel impairment in fetal rat experimental model of intestinal atresia.

Similar Datasets

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