Enteric Neurogenesis During Life Span Under Physiological and Pathophysiological Conditions

Abstract

The enteric nervous system (ENS) controls gastrointestinal key functions and is mainly characterized by two ganglionated plexus located in the gut wall: the myenteric plexus and the submucous plexus. The ENS harbors a high number and diversity of enteric neurons and glial cells, which generate neuronal circuitry to regulate intestinal physiology. In the past few years, the pivotal role of enteric neurons in the underlying mechanism of several intestinal diseases was revealed. Intestinal diseases are associated with neuronal death that could in turn compromise intestinal functionality. Enteric neurogenesis and regeneration is therefore a crucial aspect within the ENS and could be revealed not only during embryogenesis and early postnatal periods, but also in the adulthood. Enteric glia and/or enteric neural precursor/progenitor cells differentiate into enteric neurons, both under homeostatic and pathologic conditions beyond the perinatal period. The unique role of the intestinal microbiota and serotonin signaling in postnatal and adult neurogenesis has been shown by several studies in health and disease. In this review article, we will mainly focus on different recent studies, which advanced the concept of postnatal and adult ENS neurogenesis. Moreover, we will discuss the key factors and underlying mechanisms, which promote enteric neurogenesis. Finally, we will shortly describe neurogenesis of transplanted enteric neural progenitor cells. Anat Rec, 302:1345Rec, 302: -1353Rec, 302: , 2019

TGFβR-1/ALK5 inhibitor RepSox induces enteric glia-to-neuron transition and influences gastrointestinal mobility in adult mice

“…Intestinal diseases are often associated with neuronal death that could, in turn, compromise intestinal functionality [ 45 , 46 ]. Enteric neurogenesis and regeneration is therefore a crucial aspect for the recovery of ENS neuropathy.…”

Immediate Insulin Treatment Prevents Diabetes-Induced Gut Region-Specific Increase in the Number of Myenteric Serotonergic Neurons

“…In support of this, the essential role of 5-HT in the growth and maintenance of enteric neurons [46] and intestinal mucosal epithelium in adult mice were demonstrated [47]. Recent studies focus on the role of 5-HT signaling in enteric neurogenesis in adulthood both in health and diseases [48,49]. The importance of gut microbiota in maintaining the serotonergic network through release of 5-HT and the activation of the 5-HT4 receptor has also been illustrated in a recent study [50].…”

Neuron–Glia Interaction in the Developing and Adult Enteric Nervous System

“…Interactions of the gut microbiome and the ENS via the immune system is mandatory for normal functions of intrinsic and extrinsic nerves and gut-brain communication in homeostasis and allostasis [55,87,[170][171][172][173]. Direct bacterial-neuronal interaction was mediated by 5-HT, calbindin and NO [9,16,[171][172][173]. In turn, macrophages and mast cells interacted with enteric neurons via CSF and BMP 2 [87].…”