Year: 2016
Type: editorial
Abstract: ENTERIC NEURONS HAVE A HARD LIFE.Unlike their counterparts in the central nervous system, enteric neurons lack the protection against mechanical damage that a hard skull and the cushioning of cerebrospinal fluid provide.Myenteric neurons, moreover, must also endure the shearing and pressure that accompany their location between the circular and longitudinal layers of smooth muscle.Even submucosal neurons have to survive the motion of the bowel, which waxes and wanes but rarely ceases.The lumen of the gut, furthermore, contains the enteric microbiome, which may be a net plus but is also a source of invasion, defensive immune reactions, and inflammation.Inflammation, for example, has been documented to lead to an indiscriminate loss of enteric neurons (8, 11), which avaricious enteric glia aid and abet (3).Clearly, neuroprotection is essential for long-lived cells, which neurons must necessarily be, to survive in the inhospitable environment of the intestinal wall.Mechanisms of enteric neuroprotection are multiple; nevertheless, it is interesting that enteric neurons have evolved the means of using at least one of their own signaling molecules for this purpose.Serotonin is, in the adult bowel, a paracrine signal, a hormone, and a neurotransmitter (4); however, it is also a neuronal growth factor during development (10) and, by stimulating submucosal cholinergic neurons, a major promoter of the growth of the mucosal epithelium (7).Interestingly, serotonin can even stimulate neurogenesis in the mature enteric nervous system (ENS) and, in adults, serotonin promotes neurogenesis and neuroprotection through the activation of 5-HT 4 receptors (12).Curiously, serotonin is not straightforwardly a benign neuroprotective agent for enteric neurons.Mucosal serotonin is anything but that.Mucosal serotonin is strongly proinflammatory (2, 6) and, in this capacity, it is a threat to neuronal survival.Serotonin has thus been called a "sword and a shield" of the bowel (5).Mucosal serotonin is the proinflammatory sword, and neuronal serotonin is the antiinflammatory shield.The neurogenerative/neuroprotective actions of the 5-HT 4 receptor appear to be vital to maintenance of a normal ENS.Mice that lack 5-HT 4 receptors have the same number of enteric neurons as their wild-type littermates but the normal accretion of neurons that occurs through the first 4 mo of life in wild-type animals does not occur in those that lack 5-HT 4 receptors (12).In the adult bowel, neurons express 5-HT 4 receptors, which are abundant on nerve terminals as well as some cell bodies, but they are also expressed on colonic epithelial cells, where they can be accessed from the luminal surface to exert prokinetic and antinociceptive effects (9).In the current issue, Bianco et al. ( 1) report an outstanding study that clearly demonstrates the ability of the 5-HT 4 agonist prucalopride to protect enteric neurons against oxidative
Author: Michael D. Gershon
Institution: Columbia University
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2305155199