V. Genes, lineages, and tissue interactions in the development of the enteric nervous system

1998 ◽  
Vol 275 (5) ◽  
pp. G869-G873
Author(s):  
Michael D. Gershon
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Neurotrophic Factor ◽  
Protein A ◽  
Growth Factor Receptor ◽  
Enteric Neurons ◽  
Gi Tract ◽  
Tissue Interactions ◽  
Multipotent Cells ◽  
V Genes

The enteric nervous system is derived from the vagal, rostral-truncal, and sacral levels of the neural crest. Because the crest-derived population that colonizes the bowel contains multipotent cells, terminal differentiation occurs in the gut and is influenced by both the enteric microenvironment and the responsivity of multiple lineages of precursors. Enteric growth factor-receptor combinations, which promote the development of enteric neurons and/or glia in most of the gastrointestinal (GI) tract, include glial cell line-derived neurotrophic factor-GFRα-1-Ret, NT-3-TrkC, a still-to-be-identified neuropoietic cytokine-ciliary neurotrophic factor receptor-α, serotonin (5-HT)-5-HT2B, and LBP110, a 110-kDa laminin-1 binding protein. A qualitatively different effect is shown by the peptide-receptor combination ET-3-ETB, which inhibits neuronal differentiation and appears to prevent the premature differentiation of enteric neurons before colonization of the GI tract has been completed (resulting in aganglionosis of the terminal colon).

scholarly journals Hyperglycaemia-Induced Downregulation in Expression of nNOS Intramural Neurons of the Small Intestine in the Pig

2019 ◽  
Vol 20 (7) ◽  
pp. 1681 ◽  
Author(s):  
Michał Bulc ◽  
Katarzyna Palus ◽  
Michał Dąbrowski ◽  
Jarosław Całka
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Small Intestine ◽  
Enteric Nervous System ◽  
Molecular Mechanisms ◽  
Muscle Relaxation ◽  
Biologically Active ◽  
Enteric Neurons ◽  
Smooth Muscle Relaxation ◽  
Gi Tract

Diabetic autonomic peripheral neuropathy (PN) involves a broad spectrum of organs. One of them is the gastrointestinal (GI) tract. The molecular mechanisms underlying the pathogenesis of digestive complications are not yet fully understood. Digestion is controlled by the central nervous system (CNS) and the enteric nervous system (ENS) within the wall of the GI tract. Enteric neurons exert regulatory effects due to the many biologically active substances secreted and released by enteric nervous system (ENS) structures. These include nitric oxide (NO), produced by the neural nitric oxide synthase enzyme (nNOS). It is a very important inhibitory factor, necessary for smooth muscle relaxation. Moreover, it was noted that nitrergic innervation can undergo adaptive changes during pathological processes. Additionally, nitrergic neurons function may be regulated through the synthesis of other active neuropeptides. Therefore, in the present study, using the immunofluorescence technique, we first examined the influence of hyperglycemia on the NOS- containing neurons in the porcine small intestine and secondly the co-localization of nNOS with vasoactive intestinal polypeptide (VIP), galanin (GAL) and substance P (SP) in all plexuses studied. Following chronic hyperglycaemia, we observed a reduction in the number of the NOS-positive neurons in all intestinal segments studied, as well as an increased in investigated substances in nNOS positive neurons. This observation confirmed that diabetic hyperglycaemia can cause changes in the neurochemical characteristics of enteric neurons, which can lead to numerous disturbances in gastrointestinal tract functions. Moreover, can be the basis of an elaboration of these peptides analogues utilized as therapeutic agents in the treatment of GI complications.

scholarly journals The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson’s Disease

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 732
Author(s):  
Gianfranco Natale ◽  
Larisa Ryskalin ◽  
Gabriele Morucci ◽  
Gloria Lazzeri ◽  
Alessandro Frati ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Gi Tract ◽  
Multiple Control ◽  
Fine Control ◽  
The Central Nervous System ◽  
Degenerative Alterations ◽  
Comprehensive Classification

The gastrointestinal (GI) tract is provided with a peculiar nervous network, known as the enteric nervous system (ENS), which is dedicated to the fine control of digestive functions. This forms a complex network, which includes several types of neurons, as well as glial cells. Despite extensive studies, a comprehensive classification of these neurons is still lacking. The complexity of ENS is magnified by a multiple control of the central nervous system, and bidirectional communication between various central nervous areas and the gut occurs. This lends substance to the complexity of the microbiota–gut–brain axis, which represents the network governing homeostasis through nervous, endocrine, immune, and metabolic pathways. The present manuscript is dedicated to identifying various neuronal cytotypes belonging to ENS in baseline conditions. The second part of the study provides evidence on how these very same neurons are altered during Parkinson’s disease. In fact, although being defined as a movement disorder, Parkinson’s disease features a number of degenerative alterations, which often anticipate motor symptoms. Among these, the GI tract is often involved, and for this reason, it is important to assess its normal and pathological structure. A deeper knowledge of the ENS is expected to improve the understanding of diagnosis and treatment of Parkinson’s disease.

In ovo transplantation of enteric nervous system precursors from vagal to sacral neural crest results in extensive hindgut colonisation

Development ◽  
2002 ◽  
Vol 129 (12) ◽  
pp. 2785-2796 ◽  
Author(s):  
Alan J. Burns ◽  
Jean-Marie M. Delalande ◽  
Nicole M. Le Douarin
Keyword(s):  
Nervous System ◽  
Neural Crest ◽  
Enteric Nervous System ◽  
Enteric Neurons ◽  
In Ovo ◽  
Neuronal Marker ◽  
Sacral Region ◽  
Enteric Ganglia ◽  
Migration Front ◽  
Sacral Neural Crest

The enteric nervous system (ENS) is derived from vagal and sacral neural crest cells (NCC). Within the embryonic avian gut, vagal NCC migrate in a rostrocaudal direction to form the majority of neurons and glia along the entire length of the gastrointestinal tract, whereas sacral NCC migrate in an opposing caudorostral direction, initially forming the nerve of Remak, and contribute a smaller number of ENS cells primarily to the distal hindgut. In this study, we have investigated the ability of vagal NCC, transplanted to the sacral region of the neuraxis, to colonise the chick hindgut and form the ENS in an experimentally generated hypoganglionic hindgut in ovo model. Results showed that when the vagal NC was transplanted into the sacral region of the neuraxis, vagal-derived ENS precursors immediately migrated away from the neural tube along characteristic pathways, with numerous cells colonising the gut mesenchyme by embryonic day (E) 4. By E7, the colorectum was extensively colonised by transplanted vagal NCC and the migration front had advanced caudorostrally to the level of the umbilicus. By E10, the stage at which sacral NCC begin to colonise the hindgut in large numbers, myenteric and submucosal plexuses in the hindgut almost entirely composed of transplanted vagal NCC, while the migration front had progressed into the pre-umbilical intestine, midway between the stomach and umbilicus. Immunohistochemical staining with the pan-neuronal marker, ANNA-1, revealed that the transplanted vagal NCC differentiated into enteric neurons, and whole-mount staining with NADPH-diaphorase showed that myenteric and submucosal ganglia formed interconnecting plexuses, similar to control animals. Furthermore, using an anti-RET antibody, widespread immunostaining was observed throughout the ENS, within a subpopulation of sacral NC-derived ENS precursors, and in the majority of transplanted vagal-to-sacral NCC. Our results demonstrate that: (1) a cell autonomous difference exists between the migration/signalling mechanisms used by sacral and vagal NCC, as transplanted vagal cells migrated along pathways normally followed by sacral cells, but did so in much larger numbers, earlier in development; (2) vagal NCC transplanted into the sacral neuraxis extensively colonised the hindgut, migrated in a caudorostral direction, differentiated into neuronal phenotypes, and formed enteric plexuses; (3) RET immunostaining occurred in vagal crest-derived ENS cells, the nerve of Remak and a subpopulation of sacral NCC within hindgut enteric ganglia.

scholarly journals Abnormalities of the intestinal pacemaker cells, enteric neurons, and smooth muscle in intestinal atresia

2019 ◽  
Vol 11 (03) ◽  
pp. 180-185 ◽  
Author(s):  
Radhika krishna OH ◽  
Mohammed Abdul Aleem ◽  
Geetha Kayla
Keyword(s):  
Nervous System ◽  
Small Bowel ◽  
Enteric Nervous System ◽  
Gastrointestinal Motility ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Enteric Neurons ◽  
Small Bowel Atresia ◽  
Bowel Atresia ◽  
Cells Of Cajal

Abstract BACKGROUND: Small bowel atresia is a congenital disorder that carves a substantial morbidity. Numerous postoperative gastrointestinal motility problems occur. The underlying cause of this motility disorder is still unclear. Interstitial cells of Cajal (ICC) play a major role in gastrointestinal motility. AIMS AND OBJECTIVES: To investigate the morphological changes of enteric nervous system and ICC in small bowel atresia. MATERIAL AND METHODS: Resected small bowel specimen from affected patients (n=15) were divided into three parts (proximal, distal, atretic). Standard histology and immunohistochemistry with anti C-KIT receptor antibody (CD117), calretinin and α-SMA was carried out. The density of myenteric ICCs in the proximal, atretic and distal parts was demonstrated by CD 117 while Calretinin was used for ganglion cells and nerve bundles, α-SMA highlighted muscle hypertrophy. RESULT AND CONCLUSION: The proximal and distal bowel revealed clear changes in the morphology and density of enteric nervous system and interstitial cells of Cajal..

I. New insights into neuronal injury: a cautionary tale

1998 ◽  
Vol 274 (6) ◽  
pp. G978-G983 ◽  
Author(s):  
Karen E. Hall ◽  
John W. Wiley
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Cell Biology ◽  
Cell Injury ◽  
Neuronal Cell ◽  
Neuronal Injury ◽  
Molecular Techniques ◽  
Cautionary Tale ◽  
Gi Tract ◽  
Signaling Activation

Understanding of the pathophysiology of neuronal injury has advanced remarkably in the last decade. This largely reflects the burgeoning application of molecular techniques to neuronal cell biology. Although there is certainly no consensus hypothesis that explains all aspects of neuronal injury, a number of interesting observations have been published. In this brief review, we examine mechanisms that appear to contribute to the pathophysiology of neuronal injury, including altered Ca2+ signaling, activation of the protease cascades coupled to apoptosis, and mitochondrial deenergization associated with release of cytochrome c, production of free radicals, and oxidative injury. Finally, evidence for neuroprotective mechanisms that may ameliorate cell injury and/or death are reviewed. Little information has been published regarding the mechanisms that mediate injury in the enteric nervous system, necessitating a focus on models outside the gastrointestinal (GI) tract, which may provide insights into enteric nervous system injury.

scholarly journals G protein-coupled receptor trafficking and signaling: new insights into the enteric nervous system

2019 ◽  
Vol 316 (4) ◽  
pp. G446-G452 ◽  
Author(s):  
Simona E. Carbone ◽  
Nicholas A. Veldhuis ◽  
Arisbel B. Gondin ◽  
Daniel P. Poole
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
G Protein ◽  
Molecular Mechanisms ◽  
Intestinal Inflammation ◽  
Receptor Expression ◽  
Enteric Neurons ◽  
Future Research ◽  
Detailed Knowledge ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) are essential for the neurogenic control of gastrointestinal (GI) function and are important and emerging therapeutic targets in the gut. Detailed knowledge of both the distribution and functional expression of GPCRs in the enteric nervous system (ENS) is critical toward advancing our understanding of how these receptors contribute to GI function during physiological and pathophysiological states. Equally important, but less well defined, is the complex relationship between receptor expression, ligand binding, signaling, and trafficking within enteric neurons. Neuronal GPCRs are internalized following exposure to agonists and under pathological conditions, such as intestinal inflammation. However, the relationship between the intracellular distribution of GPCRs and their signaling outputs in this setting remains a “black box”. This review will briefly summarize current knowledge of agonist-evoked GPCR trafficking and location-specific signaling in the ENS and identifies key areas where future research could be focused. Greater understanding of the cellular and molecular mechanisms involved in regulating GPCR signaling in the ENS will provide new insights into GI function and may open novel avenues for therapeutic targeting of GPCRs for the treatment of digestive disorders.

scholarly journals Emerging neuropeptide targets in inflammation: NPY and VIP

2013 ◽  
Vol 304 (11) ◽  
pp. G949-G957 ◽  
Author(s):  
Bindu Chandrasekharan ◽  
Behtash Ghazi Nezami ◽  
Shanthi Srinivasan
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Enteric Nervous System ◽  
Intracellular Signaling ◽  
Enteric Neurons ◽  
Vast Number ◽  
Paracrine Effects ◽  
Intracellular Signaling Pathways ◽  
Inflammatory Processes ◽  
Epithelial Secretion

The enteric nervous system (ENS), referred to as the “second brain,” comprises a vast number of neurons that form an elegant network throughout the gastrointestinal tract. Neuropeptides produced by the ENS play a crucial role in the regulation of inflammatory processes via cross talk with the enteric immune system. In addition, neuropeptides have paracrine effects on epithelial secretion, thus regulating epithelial barrier functions and thereby susceptibility to inflammation. Ultimately the inflammatory response damages the enteric neurons themselves, resulting in deregulations in circuitry and gut motility. In this review, we have emphasized the concept of neurogenic inflammation and the interaction between the enteric immune system and enteric nervous system, focusing on neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). The alterations in the expression of NPY and VIP in inflammation and their significant roles in immunomodulation are discussed. We highlight the mechanism of action of these neuropeptides on immune cells, focusing on the key receptors as well as the intracellular signaling pathways that are activated to regulate the release of cytokines. In addition, we also examine the direct and indirect mechanisms of neuropeptide regulation of epithelial tight junctions and permeability, which are a crucial determinant of susceptibility to inflammation. Finally, we also discuss the potential of emerging neuropeptide-based therapies that utilize peptide agonists, antagonists, siRNA, oligonucleotides, and lentiviral vectors.

scholarly journals Targeting the Enteric Nervous System to Treat Metabolic Disorders? “Enterosynes” as Therapeutic Gut Factors

2019 ◽  
Vol 110 (1-2) ◽  
pp. 139-146 ◽  
Author(s):  
Claude Knauf ◽  
Anne Abot ◽  
Eve Wemelle ◽  
Patrice D. Cani
Keyword(s):  
Insulin Resistance ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Proximal Part ◽  
Enteric Neurons ◽  
Diabetic Patients ◽  
Innovative Strategy ◽  
Treatment Of Diabetes

The gut-brain axis is of crucial importance for controlling glucose homeostasis. Alteration of this axis promotes the type 2 diabetes (T2D) phenotype (hyperglycaemia, insulin resistance). Recently, a new concept has emerged to demonstrate the crucial role of the enteric nervous system in the control of glycaemia via the hypothalamus. In diabetic patients and mice, modification of enteric neurons activity in the proximal part of the intestine generates a duodenal hyper-contractility that generates an aberrant message from the gut to the brain. In turn, the hypothalamus sends an aberrant efferent message that provokes a state of insulin resistance, which is characteristic of a T2D state. Targeting the enteric nervous system of the duodenum is now recognized as an innovative strategy for treatment of diabetes. By acting in the intestine, bioactive gut molecules that we called “enterosynes” can modulate the function of a specific type of neurons of the enteric nervous system to decrease the contraction of intestinal smooth muscle cells. Here, we focus on the origins of enterosynes (hormones, neurotransmitters, nutrients, microbiota, and immune factors), which could be considered therapeutic factors, and we describe their modes of action on enteric neurons. This unsuspected action of enterosynes is proposed for the treatment of T2D, but it could be applied for other therapeutic solutions that implicate communication between the gut and brain.

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