Neuronal differentiation and myenteric plexus organization are delayed in gastroschisis: an immunohistochemical study in a rat model (original) (raw)
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Neuroscience Letters, 2004
Gastroschisis is a malformation characterized by prenatal evisceration of the midgut into the amniotic cavity. Because of the harmful effects of the amniotic fluid, the intestinal loops appear matted, thickened, and covered by a peel. At birth, the newborn presents altered intestinal motility. In a previous publication, we reported a delay in the myenteric ganglia organization and neuronal maturity in a rat model of gastroschisis. In the present study, the neurofilament formation and synaptic activity were immunohistochemically investigated in the myenteric neurons of this animal model. The expression of low, medium and high molecular weight neurofilament proteins and of a protein of the synaptic vesicles, the synaptophysin, were similar to those found at earlier embryonic ages. These findings demonstrate delayed cytoskeletal organization and reduced synaptic activity in the myenteric neurons in the rat model of gastroschisis.
Prenatal development of the myenteric plexus in the human fetal small intestine
2000
The enteric nervous system is large, complex and independent of the central nervous system. Its neural-crest-derived precursors migrate along defined pathways to colonize the bowel. It has been established that signalling molecules produced by the developing neurons and the mesenchyma of the gut wall play a critical role in the development of the mammalian enteric nervous system. Recent studies have further characterized the roles of the different cellular and molecular elements that are critical for enteric ganglia formation. The application of modern neuroanatomical techniques revealed that the enteric nervous system contains a considerable number of neuronal subpopulations. Most of our knowledge concern- ing the functional features of the enteric neurons, e.g. chemical coding, neuronal connectivity and electrophysiological behaviour, was derived from studies of the guinea-pig small intestine. In light of the interspecies differences, comparison of the findings on different specie...
Maturity of the Myenteric Plexus Is Decreased in the Gastroschisis Rat Model
Fetal Diagnosis and Therapy, 2007
ing) and immunofluorescence (␣-internexin), respectively. Results: BW was not significantly different among the control, sham and gastroschisis groups at both ages. IW and IL were larger and shorter, respectively, in the gastroschisis fetuses (p ! 0.001) at both ages. Intestinal diameters and wall layers presented significant differences among control, sham and gastroschisis fetuses at both ages (p ! 0.001), but the time of exposure to AF compromised the serous membrane, D-II (diameter II, p ! 0.001) and IL (p = 0.001). ␣-Internexin presented more intensive immunoreactivity in gastroschisis fetuses at E18.5. Conclusions: In gastroschisis, the longer the time of exposure to AF, the more severe bowel impairment will be, especially with regard to IL and the serous layer, and the more immature the myenteric plexus will be.
Morphological changes of the myenteric plexus during early postnatal development of the rat
The Anatomical record, 1999
The enteric nervous system needs to adapt itself constantly to the postnatal changes of the developing gut. The aim of this study was to examine the morphological changes between the distal and proximal segments of the gastrointestinal (GI) tract during the first two postnatal weeks. Myenteric plexus from the duodenum, proximal and distal colon of 1-, 7- and 14-day-old rat pups was dissected and examined under the scanning electron microscope. Wholemounts from the same regions and postnatal stages were stained with cuprolinic blue. Neuronal numbers per ganglionic area were counted and neuronal sizes were measured. Furthermore, segments of the above-mentioned areas were embedded in resin and semithin sections were cut. The thickness of the circular and longitudinal muscle layers was measured. The morphology of the myenteric plexus depends on localization as well as on the age of the animal. While in younger animals the myenteric plexus is usually densely packed, the network expands w...
Anatomy and Embryology, 2004
In this study, we performed a detailed topographical study on the development of ganglion plexuses and the smooth muscle layers of human embryonic and fetal gut. Neuron and glia differentiation was investigated with anti-PGP9.5 and anti-S100 antibodies respectively. The differentiation of smooth muscle and interstitial cells of Cajal (ICC) was studied with anti-smooth muscle aactin and anti-C-Kit antibodies respectively. By week 7, rostro-caudal neural crest cell (NCC) colonization of the gut was complete, and NCCs have differentiated into neurons and glia. At the foregut, neurons and glia were aggregated into ganglion plexus in the myenteric region, and the longitudinal and circular muscle layers have started to differentiate; however, neurons and glia were not found in the submucosa. At the hindgut, neurons and glia were dispersed within the mesenchyme. Myenteric plexus, longitudinal and circular muscle layers formed along the entire gut by week 9. Scattered and individual neurons and glia, and small ganglion plexuses were detected in the foregut and midgut submucosa by week 12. Ganglion plexus was not seen in the hindgut submucosa until week 14. Muscularis mucosae was formed at the foregut and midgut by week 12 but was only discernible at the hindgut 2 weeks later. As the gut wall developed, ganglion plexus increased in size with more neurons and glia, and the formation of intra-plexus nerve fascicle. ICCs were localized in the ganglion plexus as early as week 7. ICCs were initially dispersed in the plexus and were preferentially localized at the periphery of the plexus by week 20. The specification of the annular layers of human embryonic and fetal gut follows a strict spatio-temporal pattern in a rostro-caudal and centripetal manner suggesting that interaction between (1) homotypic and/or heterotypic cells; and (2) cells and the extracellular matrix is critical for the embryonic development of the gut mesenchyme and the enteric nervous system.
Microscopic Anatomy Histogenesis of enteric ganglia in human fetal stomach
2014
Introduction The Enteric nervous system (ENS) is a network which contains reflex circuits that detect the physiological condition of the gastrointestinal tract, integrate the information, and provide outputs to control gut motility, exocrine and endocrine secretions, microcirculation, immune and inflammatory processes. Elucidation of the mechanisms of ENS development and function allow the development of new approaches to the diagnosis, therapy, and prevention of human disorders of gastrointestinal motility. Therefore it is essential to understand the normal development of the ENS in human during prenatal period. This study henceforth aimed to determine the histogenesis of the enteric neurons. Materials and methods This study was done on human fetuses to evaluate the histogenesis of the enteric neurons at various gestational ages (10-28 weeks) by H&E, Masson’s Trichome Silver impregnation and immunohistochemistry for synaptophysin . Results The earliest fetus studied in the present ...
PLoS ONE, 2013
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 (6.764.6% vs 5.664.2%, p = 0.25), but proximal segments contained a higher proportion of ChAT-immunoreactive neurons (13.266.2% vs 7.564.3%, 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.
The Journal of Physiology, 2010
In mature animals, neurons and interstitial cells of Cajal (ICC) are essential for organized intestinal motility. We investigated motility patterns, and the roles of neurons and myenteric ICC (ICC-MP), in the duodenum and colon of developing mice in vitro. Spatiotemporal mapping revealed regular contractions that propagated in both directions from embryonic day (E)13.5 in the duodenum and E14.5 in the colon. The propagating contractions, which we termed ripples, were unaffected by tetrodotoxin and were present in the intestine of embryonic Ret null mutant mice, which lack enteric neurons. Neurally mediated motility patterns were first observed in the duodenum at E18.5. To examine the possible role of ICC-MP, three approaches were used. First, intracellular recordings from the circular muscle of the duodenum did not detect slow wave activity at E16.5, but regular slow waves were observed in some preparations of E18.5 duodenum. Second, spatiotemporal mapping revealed ripples in the duodenum of E13.5 and E16.5 W /W v embryos, which lack KIT+ ICC-MP and slow waves. Third, KIT-immunoreactive cells with the morphology of ICC-MP were first observed at E18.5. Hence, ripples do not appear to be mediated by ICC-MP and must be myogenic. Ripples in the duodenum and colon were abolished by cobalt chloride (1 mm). The L-type Ca 2+ channel antagonist nicardipine (2.5 μm) abolished ripples in the duodenum and reduced their frequency and size in the colon. Our findings demonstrate that prominent propagating contractions (ripples) are present in the duodenum and colon of fetal mice. Ripples are not mediated by neurons or ICC-MP, but entry of extracellular Ca 2+ through L-type Ca 2+ channels is essential. Thus, during development of the intestine, the first motor patterns to develop are myogenic.
Enteric nervous system assembly: Functional integration within the developing gut
Developmental Biology, 2016
Coordinated gastrointestinal function is the result of integrated communication between the enteric nervous system (ENS) and "effector" cells in the gastrointestinal tract. Unlike smooth muscle cells, interstitial cells, and the vast majority of cell types residing in the mucosa, enteric neurons and glia are not generated within the gut. Instead, they arise from neural crest cells that migrate into and colonize the developing gastrointestinal tract. Although they are "later" arrivals into the developing gut, enteric neural crest-derived cells (ENCCs) respond to many of the same secreted signalling molecules as the "resident" epithelial and mesenchymal cells do, and several factors that control the development of smooth muscle cells, interstitial cells and epithelial cells also regulate ENCCs. Much progress has been made towards understanding the migration of ENCCs along the gastrointestinal tract and their differentiation into neurons and glia. However, our understanding of how enteric neurons begin to communicate with each other and extend their neurites out of the developing plexus layers to innervate the various cell types lining the concentric layers of the gastrointestinal tract is only beginning. It is critical for postpartum survival that the gastrointestinal tract and its enteric circuitry are sufficiently mature to cope with the influx of nutrients and their absorption that occurs shortly after birth. Subsequently, colonisation of the gut by immune cells and microbiota during postnatal development has an important impact that determines the ultimate outline of the intrinsic neural networks of the gut. In this review, we describe the integrated development of the ENS and its target cells.