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At least 19 recordsLinked to original sources
PubMed1988

Immunohistochemical detection of GTP-binding regulatory protein (Go) in the autonomic nervous system including the enteric nervous system, superior cervical ganglion and adrenal medulla.

The localization of a GTP-binding regulatory protein, Go, in the autonomic nervous system including the enteric nervous system, superior cervical ganglion, and adrenal medulla, has been immunohistochemically examined by use of affinity-purified antibody against the alpha-subunit of Go. In the small intestine, dense Go-immunoreactive products were localized on the enteric nervous system, i.e. the myenteric plexus of Auerbach and the submucosal plexus of Meissner. In the superior cervical ganglion, presynaptic terminals were strongly immunoreactive to the Go antibody. The adrenal medulla was stained with this antibody, but the adrenal cortex was not immunoreactive to this antibody. Thus, the present study strongly suggests that Go is localized in the autonomic nervous system and plays its role in transmembrane signal transmission in this system.

Adrenal Medulla↗
PubMed1998

Mechanisms of excitatory synaptic transmission in the enteric nervous system.

The enteric nervous system can control gastrointestinal function independent of direct connections with the central nervous system. Enteric nerves can perform this task as there are multiple mechanisms of excitatory neurotransmission in enteric ganglia. There are two broad types of excitatory synaptic transmission, fast and slow excitatory synaptic responses. Fast excitatory postsynaptic potentials (fEPSPs) are recorded from "S" type neurons and some AH type neurons. S neurons are interneurons and motorneurons while AH neurons are intrinsic sensory neurons. Slow excitatory postsynaptic potentials (sEPSPs) can be recorded from some S neurons and also from AH type neurons. The fEPSPs recorded from S neurons and mediated largely by acetylcholine acting at nicotinic cholinergic receptors (nAChRs). However, ATP acting at P2X purine receptors contributes to the fEPSP in many S neurons. The fEPSPs recorded from AH neurons are also mediated largely by nAChRs but glutamate acting at AMPA receptors contributes to fEPSPs in some AH neurons. The sEPSPs in AH neurons are mediated by one or more neuropeptides and 5-hydroxytryptamine. The sEPSPs in AH neurons are due to inhibition of two types of resting potassium channels and activation of a chloride channel or a nonspecific cation channel. The multiple mechanisms of excitatory synaptic transmission in the enteric nervous system contribute to its capacity to regulate complex gastrointestinal functions.

Animals↗
PubMed2000

Multiple mechanisms of fast excitatory synaptic transmission in the enteric nervous system.

The enteric nervous system (ENS) can control gastrointestinal function independent of direct connections with the central nervous system. Enteric nerves perform this important function using multiple mechanisms of excitatory neurotransmission in enteric ganglia. Fast excitatory synaptic transmission in the autonomic nervous system (ANS) is largely mediated by acetylcholine (ACh) acting at nicotinic cholinergic receptors but in the ENS there are noncholinergic fast excitatory neurotransmitters. There are two broad types of neurons in the ENS: S neurons and AH neurons. S neurons are interneurons and motoneurons while AH neurons are sensory neurons. Three subsets of S neurons in the myenteric plexus can be distinguished on the basis of the neurotransmitters producing fast excitatory postsynaptic potentials (fEPSPs) in each subset. In one subset, fEPSPs are mediated solely by ACh acting at nicotinic cholinergic receptors. In a second subset of S neurons, ATP acting at P2X purine receptors and ACh contribute to the fEPSP while in a third subset, fEPSPs are mediated by 5-hydroxytryptamine (5-HT) acting at 5-HT(3) receptors and ACh. Some AH neurons also receive fast excitatory synaptic input. The fEPSPs recorded from AH neurons are mediated ACh and also by glutamate acting at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. Multiple mechanisms of fast excitatory synaptic transmission in the ENS are likely to contribute to its capacity to regulate complex gastrointestinal functions.

Animals↗
PubMed2002

Understanding and controlling the enteric nervous system.

The enteric nervous system or the 'Little Brain' of the gut controls gastrointestinal motility and secretion, and is involved in visceral sensation. In this chapter, new developments in understanding the function of the enteric nervous system are described. In particular, the interaction of this system with the interstitial cells of Cajal, the pacemaker cells of the gut, is highlighted. The importance of the interaction between the enteric nervous system and the immune system is discussed, especially in relation to functional bowel disorders and post-operative ileus. Evidence is also provided that neurones can change their function and phenotype, a phenomenon called neuronal plasticity, which contributes to the pathogenesis of visceral hypersensitivity. Finally, new developments in stem cell transplantation are described. All these new insights should lead to a better understanding of the enteric nervous system and hopefully to better ways of controlling it.

Coiled Bodies↗
PubMed1999

Plasticity in the enteric nervous system.

Enteric ganglia can maintain integrated functions, such as the peristaltic reflex, in the absence of input from the central nervous system, which has a modulatory role. Several clinical and experimental observations suggest that homeostatic control of gut function in a changing environment may be achieved through adaptive changes occurring in the enteric ganglia. A distinctive feature of enteric ganglia, which may be crucial during the development of adaptive responses, is the vicinity of the final effector cells, which are an important source of mediators regulating cell growth. The aim of this review is to focus on the possible mechanisms underlying neuronal plasticity in the enteric nervous system and to consider approaches to the study of plasticity in this model. These include investigations of neuronal connectivity during development, adaptive mechanisms that maintain function after suppression of a specific neural input, and the possible occurrence of activity-dependent modifications of synaptic efficacy, which are thought to be important in storage of information in the brain. One of the applied aspects of the study of plasticity in the enteric nervous system is that knowledge of the underlying mechanisms may eventually enable us to develop strategies to correct neuronal alterations described in several diseases.

Adaptation, Biological↗
PubMed2005

Control of gastrointestinal motility by the "gut brain"--the enteric nervous system.

The enteric nervous system (ENS) as the "brain of the gut" is pivotal for normal muscle activity in the gut. Neuronal circuits within the ENS are designed to control gut motility independent of central inputs. To fulfill this task the ENS contains all necessary elements for coding mechanical and chemical stimuli, interneuronal communication and efferent output to the muscle. This review provides a summary of the ENS circuits that control muscle activity, the main transmitters and neuromodulators involved and the functional implications for the normal and diseased gut.

Digestive System↗
PubMed1998

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

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-GFRalpha-1-Ret, NT-3-TrkC, a still-to-be-identified neuropoietic cytokine-ciliary neurotrophic factor receptor-alpha, 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).

Animals↗
PubMed1999

Genesis and role of coordinated firing in a feedforward network: a model study of the enteric nervous system.

The enteric nervous system can generate complex motor patterns independently of the central nervous system. The ascending enteric reflex pathway consists of sensory neurons, long chains of a single class of orally directed interneuron and excitatory motor neurons. Because of the importance of this pathway in peristalsis, it was modelled from the firing of sensory neurons through to muscle membrane activation. The model was anatomically realistic in the number of neurons simulated and in the patterns of connections between neurons. The model was also realistic in the simulation of ligand-gated currents in neuron and muscle membrane, current flow in the muscle syncytium and voltage-dependent currents in muscle. Sensory neurons were activated in a manner consistent with a brief mechanical stimulus. Transmission between sensory neurons and first-order interneurons was by slow excitatory transmission, which caused interneurons to fire continuously for several hundred milliseconds. Interneurons then transmitted to higher order interneurons by fast excitatory postsynaptic potentials, each lasting for around 40 ms. As the activity propagated along the pathway, random firing became progressively more synchronized between neurons, until the network as a whole was firing in a coordinated manner. The coordinated firing was a robust phenomenon over a wide range of network and neuron parameters. It is therefore possible that this is a general property of feedforward networks that receive high levels of sustained input. The smooth muscle model indicated that bursting input to the muscle may increase the likelihood of muscle cells firing action potentials when compared with uniform input. In addition, the syncytium model explains how the predicted muscle excitation might be related to current experimental observations.

Action Potentials↗
PubMed2005

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. Moreover, functional BMP signaling, demonstrated by the expression of phosphorylated Smad1/5/8, is present in the enteric ganglia. Inhibition of BMP activity by noggin misexpression within the developing gut, both in ovo and in vitro, inhibits normal migration of enteric neural crest cells. BMP inhibition also leads to hypoganglionosis and failure of enteric ganglion formation, with crest cells unable to cluster into aggregates. Abnormalities of migration and ganglion formation are the hallmarks of two human intestinal disorders, Hirschsprung's disease and intestinal neuronal dysplasia. Our results support an essential role for BMP signaling in these aspects of ENS development and provide a basis for further investigation of these proteins in the etiology of neuro-intestinal disorders.

Animals↗
PubMed2003

Localization and function of metabotropic glutamate receptor 8 in the enteric nervous system.

The enteric nervous system (ENS) contains glutamatergic neurons, transporters, and functional ionotropic and groups I and II metabotropic glutamate receptors (mGluRs). The aim of this study was to determine whether the ENS contains functional group III mGluRs. RT-PCR demonstrated the expression of mGluR7 and mGluR8 mRNA in rat myenteric ganglia. Western blot analysis confirmed the presence of mGluR8 protein. Immunocytochemistry, in conjunction with confocal microscopy, demonstrated mGluR8 immunoreactivity in the ENS of several species, including humans. mGluR8 immunoreactivity was localized to the membrane of nerve cell bodies that received glutamatergic input. Significant receptor internalization of mGluR8 was observed on activation, and localization to membrane was observed on blocking with the mGluR III antagonist (RS)-cyclopropyl-4-phosphonophenylglycine (CPPG). mGluR8-positive myenteric neurons contained glutamate or nitric oxide synthase (NOS), a marker of inhibitory motorneurons. Enteric group III mGluRs are functional because mGluR8 agonists inhibited forskolin-induced accumulation of cAMP in isolated myenteric ganglia, and CPPG reduced this effect. In addition, an accelerating effect on guinea pig colonic motility was observed after the application of mGluR8 agonists. Increase in motility was specific, because CPPG inhibited it. Moreover, in the presence of hexamethonium or Nomega-nitro-l-arginine methyl ester, an inhibitor of NOS, responses caused by mGluR8 agonists were abolished. mGluR8 agonists also increased longitudinal muscle contractions. These findings suggest that mGluR8 agonists increase motility by inhibiting nitrergic relaxation and possibly by facilitating cholinergic contractions.

Animals↗
PubMed2003

Differentiation of neurospheres from the enteric nervous system.

The enteric nervous system (ENS) derives from neural crest cells, which migrate from the neural tube into the developing gut. The neuronal and glial precursor cells migrate mainly from the oral towards the anal end of the gastrointestinal tract. So far, knowledge about the multipotent influences upon the ENS development, especially its neurotrophic support, derives mainly from knock-out models. The in vitro technique of isolating enteric neuronal precursor cells allows to study the effects of various factors upon their appropriate development in more detail. We therefore adapted the method of growing neurospheres, which are agglomerates of neuronal precursor cells and differentiated neurones and glial cells, from the central nervous system (CNS) for the ENS. The gut of NMRI mice at E12 were dissected, mildly dissociated and plated in 25-cm(2) culture flasks. The cultures were maintained in N1 supplemented DMEM/F12 medium with the appropriate neurotrophin cocktails (bFGF, GDNF, Neurturin, CNTF). After several days in culture most of the cells die, while the surviving cells form clusters from which domes, and later spheres arise. The spheres could be harvested and processed for further experiments. First investigations revealed, that the amount of precursor cells was much less in enteric neurospheres as seen in corresponding cultures from the CNS. We found about 43% HNK-1-NCAM+ in enteric and approximately 90% Nestin-+ cells in midbrain neurospheres. Differentiation studies of the enteric neurospheres showed that especially ciliary neurotrophic factor (CNTF) increased the number of enteric neurones (PGP positive), while the amount of HNK-1 precursor cells decreased under the influence of all tested neurotrophins but GDNF. The culture of the freshly dissociated enteric neurospheres in a three-dimensional matrix yielded a secondary network which allows to investigate the pattern formation of the ENS. The generation of enteric neurospheres and the following differentiation and 3D culture in vitro can increase our knowledge of the amount and time point of neurotrophic as well as the ECM-protein influence upon the appropriate development of the ENS.

Animals↗
PubMed1997

Genes and lineages in the formation of the enteric nervous system.

The enteric nervous system is large, complex, and independent of the CNS. Its neural-crest-derived precursors migrate along defined pathways to colonize the bowel. Recent studies of the sequential actions of essential growth and transcription factors have revealed that enteric neuronal development involves a complex interaction of lineage-determined and microenvironmental elements.

Animals↗
PubMed1980

Peptide-containing neurones connect the two ganglionated plexuses of the enteric nervous system.

The enteric nervous system (ENS) of the mammalian gut consists principally of two ganglionated plexuses, the myenteric and submucous, which are embedded in the gut wall. Little is known about the anatomical and functional connections between the two plexuses and further clarification of their relationship is of central importance for the understanding of the ENS. In the present study we have approached this problem in a new way, using methods we have previously developed for maintaining the myenteric and submucous plexuses separately in vitro for several weeks. In an immunohistochemical study of these preparations and also of sections from normal and extrinsically denervated gut wall, we have found evidence for reciprocal projections between the myenteric and submucous plexuses, by nerve fibres containing two putative neurotransmitters, vasoactive intestinal polypeptide (VIP) and substance P (ref. 5) (see Fig. 1). Our observations were supported by radioimmunoassay of tissue extracts. These results suggest that one of the roles of these peptides in the gut is to coordinate the function of the two enteric plexuses.

Animals↗
PubMed1998

III. Role Of the RET signal transduction pathway in development of the mammalian enteric nervous system.

The enteric nervous system (ENS) in vertebrates is derived from the neural crest and constitutes the most complex part of the peripheral nervous system. Natural and induced mutagenesis in mammals has shown that the tyrosine kinase receptor RET and its functional ligand glial cell line-derived neurotrophic factor (GDNF) play key roles in the development of the ENS in humans and mice. We have developed and briefly describe here a number of assays that analyze the specific function of the RET receptor and its ligand. Our data suggest that the RET signal transduction pathway has multiple roles in the development of the mammalian ENS.

Animals↗
PubMed2007

Genetic screen for mutations affecting development and function of the enteric nervous system.

An intact enteric nervous system is required for normal gastrointestinal tract function. Several human conditions result from decreased innervation by enteric neurons; however, the genetic basis of enteric nervous system development and function is incompletely understood. In an effort to increase our understanding of the mechanisms underlying enteric nervous system development, we screened mutagenized zebrafish for changes in the number or distribution of enteric neurons. We also established a motility assay and rescreened mutants to learn whether enteric neuron number is correlated with gastrointestinal motility in zebrafish. We describe mutations isolated in our screen that affect enteric neurons specifically, as well as mutations that affect other neural crest derivatives or have pleiotropic effects. We show a correlation between the severity of enteric neuron loss and gastrointestinal motility defects. This screen provides biological tools that serve as the basis for future mechanistic studies.

Animals↗
PubMed2004

Transient expression of NOS-II during development of the murine enteric nervous system.

In the enteric nervous system, nitric oxide (NO) is regarded as an important messenger for the non-adrenergic and non-cholinergic neurotransmission. Synthesized mainly by the constitutive nitric oxide synthase (NOS) isoforms NOS I and NOS III, this molecule exerts prejunctional inhibitory effects in the submucosal plexus as well as relaxation of enteric smooth muscles. In order to elucidate the role for NO during enteric development, we looked for the expression of all three NOS-isoforms in the enteric nervous system during mouse development from E8 to E20 using immunohistochemistry. Starting around midgestation, a transient expression of the NOS-II isoform during the very early development of enteric neurones was detected in parallel to that of HNK-1 exclusively in the myenteric plexus. Similar to findings for other neuronal systems, NOS-I and NOS III isoforms could be traced starting significantly later to increase toward the end of embryonic development when NOS II immunoreactivity faded and a strong expression of the vasointestinal peptide could be detected. In contrast to the NOSII expression, the constitutive isoforms can also be detected in the submucosal plexus. Altogether, these findings suggest NOS-II to be exclusively involved during early steps of enteric nervous system development. Absence of downstream signalling elements, such as sGC and cGMP both in neurons and in enteric muscle until the end of the second third of gestation, may indicate different effects executed by NO during development, expressed by Ca(2+) -dependent and Ca(2+) -independent NOS isoforms.

Animals↗
PubMed1986

Zuelzer-Wilson's syndrome and absence of the enteric nervous system. Two rare forms of anomalies of the enteric nervous system with identical clinical symptoms.

47 children have been treated in Basel for aganglionosis (Hirschsprung's disease) during the last 25 years. Six children presented severe vomiting and an ileus as leading symptoms instead of chronic constipation, the classical leading symptom of Hirschsprung's disease. Clinical, radiological and intraoperative findings were virtually identical in these 6 patients. However, enzyme histochemical and immunocytochemical investigations disclosed an aganglionosis of the entire colon (Zuelzer-Wilson's disease) in 3 patients, absence of the enteric nervous system in the small and large intestine in 2 patients, and a combination of both in 1 patient. In contrast to children suffering from aganglionosis of the entire colon, the chance of survival for patients with an absence of the enteric nervous system is extremely small. It is therefore necessary in presence of severe vomiting and an ileus to take intraoperative biopsies from the large and the small intestine. The precise diagnosis can be made only by using enzyme histochemical and immunocytochemical techniques.

Cholinergic Fibers↗
PubMed1999

Development of the mammalian enteric nervous system.

The mammalian enteric nervous system is derived from neural crest cells which invade the foregut and hindgut mesenchyme. It has been established that signalling molecules produced by the mesenchyme of the gut wall play a critical role in the development of the mammalian enteric nervous system. Recent studies have characterised further the role of such molecules and have identified novel extracellular and intracellular signals that are critical for enteric ganglia formation.

Animals↗