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BMP signaling is necessary for neural crest cell migration and ganglion formation in the enteric nervous system.

The enteric nervous system (ENS) is derived from neural crest cells that migrate along the gastrointestinal tract to form a network of neurons and glia that are essential for regulating intestinal motility. Despite the number of genes known to play essential roles in ENS development, the molecular etiology of congenital disorders affecting this process remains largely unknown. To determine the role of bone morphogenetic protein (BMP) signaling in ENS development, we first examined the expression of bmp2, bmp4, and bmprII during hindgut development and find these strongly expressed in the ENS. …

Anatomic modifications in the enteric nervous system of piebald mice and physiological consequences to colonic motor activity.

It has been assumed that in piebald lethal mice that develop megacolon, impaired colonic motor activity is restricted to the aganglionic distal colon. Peristaltic mechanical recordings, immunohistochemistry, and quantitative PCR were used to investigate whether regions of the colon, other than the aganglionic segment, may also show anatomical modifications and dysfunctional colonic motor activity. Contrary to expectations, colonic migrating motor complexes (MMCs) were absent along the whole colon of piebald lethal homozygote mice and severely impaired in heterozygote siblings. Aganglionosis wa

Morphological investigation of the enteric nervous system in Hirschsprung's disease and hypoganglionosis using whole-mount colon preparation.

BACKGROUND/PURPOSE: A suction rectal mucosal biopsy with positive staining for acetylcholinesterase is a useful test for diagnosis of Hirschsprung's disease (HD). However, hypoganglionosis has not been diagnosed by a rectal mucosal biopsy. The authors morphologically examined the enteric nervous systems in HD and hypoganglionosis patients using whole-mount preparations. METHODS: Six HD patients, two hypoganglionosis patients, and 10 with normally innervated colons were examined. Colonic specimens were incubated with the primary antibodies against protein gene product 9.5 (PGP 9.5) mixed with …

Diagnosis of innervation-related motility disorders of the gut and basic aspects of enteric nervous system development.

Motility disorders of the gut in children have become a matter of increasing concern for the pediatric surgeon. Infantile hypertrophic pylor … ult of anomalies of the intestinal innervation. The pathogenesis of congenital malformations of the enteric nervous system is still a mystery to surgeons and physicians alike. With his pressure studies of the colon, Swenson first recognized Hirschsprung's disease for what it was. This led to the resection of the manometrically diagnosed abnormal colon, which was found t …

Abnormal Enteric Nervous System Organization and Gastrointestinal Motility in Mice With Valproic Acid-Induced Neural Tube Defects.

BACKGROUND: Neural tube defects (NTDs) are a common congenital birth anomaly that can occur at either cranial levels, resulting in anencephaly, or spinal levels, resulting in spina bifida. Neurogenic bowel is a major cause of morbidity in patients affected by spina bifida, but it is unknown whether the gastrointestinal (GI) tract is affected in other types of NTDs. An absolute requirement for GI motility is the enteric nervous system (ENS) located within the walls of the GI tract. Enteric neurons coalesce into circumferential stripes throughout embryonic, fetal, and early postnatal development…

Neurochemical Remodelling of the Enteric Nervous System Neurons in the Porcine Jejunum Following Low-Dose Glyphosate Exposure.

Glyphosate, a widely used herbicide, is under scrutiny for its potential neurotoxic effects. This study investigated whether oral exposure to glyphosate, even at doses currently considered safe in Europe, alters the neurochemical profile of enteric nervous system (ENS) neurons in the porcine jejunum. Fifteen immature female pigs were allocated to three groups: control (C), low-dose (G50; 50 µg/kg b.w./day), and higher-dose (G500; 500 µg/kg b.w./day). Following 28 days of exposure, jejunal samples were subjected to double-labelling immunofluorescence staining for neuronal markers, including Hu …

Иммунизация с говяжьим молоком дает результаты в патологии системы электронно-нервоза в модели мыши нейроинфламмации.

Множественный склероз (MS) — иммунопосредованное демиелинирующее заболевание центральной нервной системы (CNS) с признаками аутоиммунной атаки на интестинальную нервную систему (ENS). Ранее обсуждалась роль различных антигенов рациона питания, включая белки говядины, в усилении симптомов MS. В модели мыши нейроинфламмации мы описали масштабы патологии ЭНС у животных, которым были сделаны прививки различными антигенами говядинного молока с использованием электронной микроскопии, иммуногистохимии, молекулярной биологии и клеточной культуры в качестве ключевых методов.Наши данные свидетельствуют

Совпадение в аннотации оригинала
BACKGROUND: Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) with evidence of autoimmune attack also on the enteric nervous system (ENS). The role of different dietary antigens, including bovine milk proteins, in the exacerbation of MS symptoms has previously been discussed. METHODS: In a mouse model of…

Immune landscape of the enteric nervous system differentiates Parkinson's disease patients from controls: The PADUA-CESNE cohort.

BACKGROUND: Gastrointestinal dysfunction has emerged as a prominent early feature of Parkinson's Disease, shedding new light on the pivotal role of the enteric nervous system in its pathophysiology. However, the role of immune-cell clusters and inflammatory and glial markers in the gut pathogenetic process needs further elucidation. OBJECTIVES: We aimed to study duodenum tissue samples to characterize PD's enteric nervous system pathology further. Twenty patients with advanced PD, six with early PD, and 18 matched controls were included in the PADUA-CESNE cohort. METHODS: Duodenal biopsies f…

A targeted CRISPR-Cas9 mediated F0 screen identifies genes involved in establishment of the enteric nervous system.

The vertebrate enteric nervous system (ENS) is a crucial network of enteric neurons and glia resident within the entire gastrointestinal tract (GI). Overseeing essential GI functions such as gut motility and water balance, the ENS serves as a pivotal bidirectional link in the gut-brain axis. During early development, the ENS is primarily derived from enteric neural crest cells (ENCCs). Disruptions to ENCC development, as seen in conditions like Hirschsprung disease (HSCR), lead to the absence of ENS in the GI, particularly in the colon. In this study, using zebrafish, we devised an in vivo F0 …

Colorectal Cancer Invasion and Atrophy of the Enteric Nervous System: Potential Feedback and Impact on Cancer Progression.

Colorectal cancer (CRC) invasion within the large intestine wall results in the replacement of normal tissue architecture by tumour mass. Ca … n the local tumour microenvironment. Cancer invasion destroys nerve fibres and neurons of the local enteric nervous system (ENS) and induces subsequent atrophy of the submucosal and myenteric plexuses in areas adjacent to the cancer boundary. Interestingly, the reduction of plexuses' size is accompanied by the increased number of galanin-immunoreactive neurons and incre …

Alterations in Galanin-Like Immunoreactivity in the Enteric Nervous System of the Porcine Stomach Following Acrylamide Supplementation.

In recent years, a significant increase in the consumption of products containing large amounts of acrylamide (e.g., chips, fries, coffee), … GAL and possible co-operation of GAL with VIP, nNOS, CART in the recovery processes in the stomach enteric nervous system (ENS) neurons following acrylamide intoxication.

Characterisation of tau in the human and rodent enteric nervous system under physiological conditions and in tauopathy.

Tau is normally a highly soluble phosphoprotein found predominantly in neurons. Six different isoforms of tau are expressed in the adult human CNS. Under pathological conditions, phosphorylated tau aggregates are a defining feature of neurodegenerative disorders called tauopathies. Recent findings have suggested a potential role of the gut-brain axis in CNS homeostasis, and therefore we set out to examine the isoform profile and phosphorylation state of tau in the enteric nervous system (ENS) under physiological conditions and in tauopathies. Surgical specimens of human colon from controls, Pa…

Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse.

Hirschsprung Disease (HSCR) is a potentially deadly birth defect characterized by the absence of the enteric nervous system (ENS) in distal bowel. Although HSCR has clear genetic causes, no HSCR-associated mutation is 100% penetrant, suggesting gene-gene and gene-environment interactions determine HSCR occurrence. To test the hypothesis that certain medicines might alter HSCR risk we treated zebrafish with medications commonly used during early human pregnancy and discovered that ibuprofen caused HSCR-like absence of enteric neurons in distal bowel. Using fetal CF-1 mouse gut slice cultures, w…

Identification of GLI Mutations in Patients With Hirschsprung Disease That Disrupt Enteric Nervous System Development in Mice.

BACKGROUND & AIMS: Hirschsprung disease is characterized by a deficit in enteric neurons, which are derived from neural crest cells (NCCs). … ere tested in luciferase reporter assays using HeLa or neuroblastoma cell lines. Development of the enteric nervous system was studied in Sufu(f/f), Gli3(Δ699), Wnt1-Cre, and Sox10(NGFP) mice using immunohistochemical and whole-mount staining procedures to quantify enteric neurons and glia and analyze axon fasciculation, respectively. NCC migration was studied using tim …

Changes of the enteric nervous system in amyloid-β protein precursor transgenic mice correlate with disease progression.

In Alzheimer's disease (AD), fatal neuronal cell loss occurs long before relevant evidence can lead to a reliable diagnosis. If characteristic pathological alterations take place in the enteric nervous system (ENS), it could be one of the most promising targets for an early diagnosis, using submucosal biopsies from the gut. We therefore investigated time- and spatial-dependent changes in an amyloid-β protein precursor (AβPP) overexpressing transgenic mouse model to examine early changes within the ENS. Wholemount preparations and paraffin sections were analyzed for the expression of neuronal, …

Characteristic of galaninergic components of the enteric nervous system in the cancer invasion of human large intestine.

BACKGROUND: This study presents changes that take place in galanin (GAL)-containing components of the enteric nervous system in patients with colorectal carcinoma. The main goal of our study was to investigate the morphological and biochemical characteristics of the GAL-ergic neurons and nerve fibers in the cancer-affected part of the colon and to compare results to the unchanged part of the intestine. MATERIAL AND METHODS: The study was performed on tissue samples collected from 15 patients (9 women and 6 men). The material was collected during surgery, i.e., resection of the anterior sigmoi…

Enteric nervous system stem cells derived from human gut mucosa for the treatment of aganglionic gut disorders.

BACKGROUND & AIMS: Enteric nervous system stem cells (ENSSCs) provide potential therapeutic tools to replenish absent ganglia in Hirschsprung's disease. Although full-thickness human postnatal gut tissue can be used to generate ENSSCs, reliance on its harvesting from surgical resection poses significant practical limitations. This study aimed to explore whether gut tissue obtained utilizing minimally invasive routine endoscopy techniques could be used to generate ENSSCs and whether such cells retain the potential to generate an ENS upon transplantation into aganglionic gut. METHODS: Postnatal…

The galaninergic enteric nervous system of pleuronectiformes (Pisces, Osteichthyes): an immunohistochemical and confocal laser scanning immunofluorescence study.

The galaninergic enteric nervous system of three flatfishes was studied using immunohistochemical and immunofluorescence methods. Galanin-like immunoreactivity was mainly detected within the enteric intramural neurons of the stomachs and the proximal intestines. The sole, Solea solea L. and the flounder, Platichthys flesus L. showed a similar occurrence and relative distribution of galaninergic intramural neurons. Rare nervous fibre immunoreactive to the anti-galanin serum were observed in the muscular layers of the oesophagus of the turbot, Psetta maxima L. The presence and relative abundance…

Distribution and chemical coding of corticotropin-releasing factor-immunoreactive neurons in the guinea pig enteric nervous system.

Immunofluorescence was used to study immunoreactivity (IR) for corticotropin-releasing factor (CRF) in the guinea pig enteric nervous system. CRF-IR was expressed in both the myenteric and the submucosal plexuses of all regions of the large and small intestine and the myenteric plexus of the stomach. CRF-IR nerve fibers were present in the myenteric and submucosal plexuses, in the circular muscle coat, and surrounding submucosal arterioles. Most of the CRF-IR fibers persisted in the myenteric and submucosal plexuses after 7 days in organotypic culture. CRF-IR was not coexpressed with tyrosine …

Differential gene expression and functional analysis implicate novel mechanisms in enteric nervous system precursor migration and neuritogenesis.

Enteric nervous system (ENS) development requires complex interactions between migrating neural-crest-derived cells and the intestinal microenvironment. Although some molecules influencing ENS development are known, many aspects remain poorly understood. To identify additional molecules critical for ENS development, we used DNA microarray, quantitative real-time PCR and in situ hybridization to compare gene expression in E14 and P0 aganglionic or wild type mouse intestine. Eighty-three genes were identified with at least two-fold higher expression in wild type than aganglionic bowel. ENS expre…