Neurobiology of Human Enteric Nervous System (original) (raw)

Building a brain in the gut: development of the enteric nervous system

Clinical Genetics, 2013

The enteric nervous system (ENS), the intrinsic innervation of the gastrointestinal tract, is an essential component of the gut neuromusculature and controls many aspects of gut function, including coordinated muscular peristalsis. The ENS is entirely derived from neural crest cells (NCC) which undergo a number of key processes, including extensive migration into and along the gut, proliferation, and differentiation into enteric neurons and glia, during embryogenesis and fetal life. These mechanisms are under the molecular control of numerous signaling pathways, transcription factors, neurotrophic factors and extracellular matrix components. Failure in these processes and consequent abnormal ENS development can result in so-called enteric neuropathies, arguably the best characterized of which is the congenital disorder Hirschsprung disease (HSCR), or aganglionic megacolon. This review focuses on the molecular and genetic factors regulating ENS development from NCC, the clinical genetics of HSCR and its associated syndromes, and recent advances aimed at improving our understanding and treatment of enteric neuropathies. Keywords enteric nervous system; Hirschsprung disease; enteric neuropathies; neural crest cells; RET A functional gastrointestinal (GI) tract is essential for transporting, absorbing, digesting, and excreting food and waste, for protecting the host from ingested pathogens, allergens, and toxins, and for continuously monitoring and responding to the state of the intestinal lumen. The principal conductor of this highly orchestrated symphony is the enteric nervous system (ENS), a vast and complex network of neurons and glial cells that is located along the length of the GI tract and represents an important component of the autonomic nervous system (1). While extrinsic innervation from the central nervous system can modulate ENS function, the ENS serves as an intrinsic nervous system for the gut, capable of controlling most of the functions of the intestine independently. It is because of its complexity and autonomous function that the ENS is often referred to as the `second brain' (2).

Enteric nervous system, gut-brain connection and related neurodevelopmental disorders (Review paper)

Anatomy, 2020

When compared to other peripheral organs of the body, the gastrointestinal tract (GIT) differs from all of them. GIT has a comprehensive internal nervous system called enteric nervous system (ENS), which can control intestinal function, even if it is totally cut off from the central nervous system (CNS). [1] The ENS provides unique innervation of the intestine and is the most neurochemically diverse part of the peripheral nervous system (PNS). [2] The ENS was described by British physiologist John Newport Langley as one of the three autonomic nervous system parts: parasympathetic nervous system, enteric nervous system and sympathetic nervous system. [3] More than 100 million efferent neurons that reach the intestines through the vagus nerve are present in human ENS. [4] Unlike the rest of the PNS, the complexity of managing bowel behavior is a privilege that evolution provides to the ENS, which has led to the ability to manifest complementary neuronal activity and to control gastrointestinal behavior independently of the brain or spinal cord. [5-7] The ENS has at least as many neurons as in the spinal cord but has more neurons than any other group of peripheral ganglia. Unique to PNS, the ENS is regulated in microcircuits with intrinsic primary afferent neurons (IPANs) and interneurons that are capable of initiating reflexes. The phenotypic diversity of enteric neurons is very wide and almost every class of neurotransmitters found in the CNS has been identified in the ENS. [6] Although the ENS can work independently from the CNS, it normally does not; CNS affects the enteric system and the intestine also sends information to the brain. Indeed, 90% of the vagal fibers between the intestine and the brain are afferent, suggesting that the brain is more recipient than a giver in brainintestinal communication. [6,8] ENS is located within the tubular digestive system walls, biliary system and pancreas. ENS has myenteric and submucosal plexuses, two ganglioned plexuses in the intestine, where almost all intrinsic nerve cells are present. [9] The myenteric plexus is located between the outer longi

Enteric Nervous System: Development and Developmental Disturbances--Part 2

Pediatric and Developmental Pathology, 2002

This review, which is presented in two parts, summarizes and synthesizes current views on the genetic, molecular, and cell biological underpinnings of the early embryonic phases of enteric nervous system (ENS) formation and its defects. In the first part, we describe the critical features of two principal abnormalities of ENS development: Hirschsprung's disease (HSCR) and intestinal neuronal dysplasia type B (INDB) in humans, and the similar abnormalities in animals. These represent the extremes of the diagnostic spectrum: HSCR has agreed and unequivocal diagnostic criteria, whereas the diagnosis and even existence of INDB as a clinical entity is highly controversial. The difficulties in diagnosis and treatment of both these conditions are discussed. We then review the genes now known which, when mutated or deleted, may cause defects of ENS development. Many of these genetic abnormalities in animal models give a phenotype similar or identical to HSCR, and were discovered by studies of humans and of mouse mutants with similar defects. The most important of these genes are those coding for molecules in the GDNF intercellular signaling system, and those coding for molecules in the ET-3 signaling system. However, a range of other genes for different signaling systems and for transcription factors also disturb ENS formation when they are deleted or mutated. In addition, a large proportion of HSCR cases have not been ascribed to the currently known genes, suggesting that additional genes for ENS development await discovery.

Enteric Nervous System: A Review

2015

Enteric nervous system directs and regulates the breakdown, absorption and elimination of food in our digestive system. However, alongside its digestive functions, enteric nervous system has also gained importance because of the discovery of its bidirectional link with intestinal flora, which has recently started to be considered as a separate organ in addiction to its digestive functions. Enteric nervous system contains approximately 100 million nerve cells, operates both independently and in coordination with the central nervous system, interacts with many neurotransmitters and is related to many conditions and structures such as the intestinal flora, mood, immune system and the efficiency of food utilization. It has a clinical importance on account of the diseases it is associated with. Recent studies focus on the connections between the intestinal flora, enteric nervous system and mechanisms of disease development. In order to understand these studies and pathological mechanisms...

Enteric Nervous System and Its Internal Structure

2020

The vagus nerve is the primary neural medium which enables gastrointestinal tract and brain communication. Hippocampus, a region of the brain commonly linked to memory function, is activated by vagus nerve-mediated gastrointestinal signals. Vagal afferent information is received by the medial solitary nucleus and is then transmitted via ascending neural pathways to different regions of the forebrain and hindbrain. Explanation of the exact mechanisms of microbiota and amygdala communication requires further research. By linking microbial activities to progressive structural and functional events in the brain in mice models and in humans, we can suggest that intestinal microbiota is an important contributor to neurodevelopment and neurodegeneration. Further researches revealing these relations may provide new approaches for understanding neurodegenerative, psychiatric and behavioral diseases.

The gut as a neurological organ

Wiener Klinische Wochenschrift, 2001

Wir bezeichnen den Gastrointestinaltrakt als neurologisches Organ, um die spezielle Rolle des Nervensystems bei der Steuerung der Verdauung hervorzuheben, wird der Magen-Darm-Trakt doch von fünf verschiedenen Neuronensystemen versorgt: intrinsische enterale Neurone, vagale und spinale afferente Neurone sowie parasympathische und sympathische efferente Neurone. Praktisch jeder Aspekt der Verdauungstätigkeit steht unter neuraler Kontrolle, wobei das enterale Nervensystem (ENS) die wichtigste Rolle spielt. Das ENS funktioniert wie ein Gehirn im Darm, da es unabhängig vom Zentralnervensystem die Verdauungsvorgänge programmiert und die Tätigkeit der gastrointestinalen Effektorsysteme bedarfsgerecht koordiniert. Zu diesem Zweck liefern intrinsische afferente Neurone dem ENS entsprechende Informationen aus dem Lumen, während extrinsische afferente Neurone das Zentralnervensystem über den Funktionszustand des Gastrointestinaltrakts informieren und damit zur Energie-und Flüssigkeitshomöostase des Körpers beitragen, jedoch auch die Wahrnehmung gastrointestinaler Funktionsstörungen und Schmerzen vermitteln. Die meisten funktionellen Magen-und Darmerkrankungen hängen mit einer Dysfunktion des ENS und anderer gastrointestinaler Neuronensysteme zusammen. Aus diesem Grund stellen enterale und extrinsische afferente Neurone des Gastrointestinaltrakts einen besonders wichtigen Angriffspunkt für die medikamentöse Behandlung von Magen-und Darmkrankheiten und für die damit verbundenen Beschwerden und Schmerzen dar.

The Brain-Like Enteric Nervous System

Physiology

Understanding the autonomic supply at the gastrointestinal tract is one of the significant challenges for science. Its complex network of neurons exists on a broad evolutionary scale, from Hydra to mammals, and in a higher number than those found in the vertebrate spinal cord. Inside the gastrointestinal tract, enteric neurons regulate several functions with intrinsic processes and communicate with the other complex known as the microbiome. Outside the gastrointestinal tract, the enteric neurons project to the brain stem and spinal cord via the gut–brain axis. Furthermore, this enteric system has close functional relationships with the immune system for a rapid response to unhealthy food. The present chapter focuses on the structure, function, and pathologies of the enteric nervous system.

The Enteric Nervous System: A Second Brain

Hospital Practice, 1999

Once dismissed as a simple collection of relay ganglia, the enteric nervous system is now recognized as a complex, integrative brain in its own right. Although we still are unable to relate complex behaviors such as gut motility and secretion to the activity of individual neurons, work in that area is proceeding briskly-and will lead to rapid advances in the management of functional bowel disease.