Essential Roles of Enteric Neuronal Serotonin in Gastrointestinal Motility and the Development/Survival of Enteric Dopaminergic Neurons

Li, Zhishan; Chalazonitis, Alcmène; Huang, Yung‐yu; Mann, J. John; Margolis, Kara Gross; Yang, Qi; Kim, Dolly O.; Côté, Francine; Mallet, Jacques; Gershon, Michael D.

doi:10.1523/jneurosci.6684-10.2011

Cited by 342 publications

(397 citation statements)

References 73 publications

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“…Li and colleagues studied Tph1−/−, Tph2−/− or double KOs to identify the role of neuronal vs nonneuronal 5-HT in the gut. 42 Their results were quite surprising and revealed that peripheral 5-HT (Tph1-derived 5-HT: ∼95% of gut 5-HT content) has only a very minor role in regulation of GI motility in the mouse, while neuronal (Tph2 derived 5-HT: ∼5% of gut 5-HT content) has a much more considerable role than previously believed. Tph1 KO mice did not differ from controls in GI functions measured (gastric emptying, total intestinal transit, and colonic motility.…”

Section: ■ Tph1-derived Serotonin In the Gut: What Does It Really Do?mentioning

confidence: 96%

“…Tph1 KO mice did not differ from controls in GI functions measured (gastric emptying, total intestinal transit, and colonic motility. 42 In comparison, Tph2 KO animals had major changes in each function and the double KOs were indistinguishable from Tph2-null mice. The results of Li et al indicate that Tph1-derived 5-HT is trivial for normal GI motility.…”

Section: ■ Tph1-derived Serotonin In the Gut: What Does It Really Do?mentioning

confidence: 96%

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Life without Peripheral Serotonin: Insights from Tryptophan Hydroxylase 1 Knockout Mice Reveal the Existence of Paracrine/Autocrine Serotonergic Networks

Amireault

Sibon

Côté

2012

ACS Chem. Neurosci.

135

113

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Since its identification, 75 years ago, the monoamine serotonin (5-HT) has attracted considerable attention toward its role as a neurotransmitter in the central nervous system. Yet, increasing evidence, from a growing number of research groups, substantiates the fact that 5-HT regulates important nonneuronal functions. Peripheral 5-HT, synthesized by the enzyme tryptophan hydroxyase (Tph) in intestinal cells, was assumed to be distributed throughout the entire body by blood platelets and to behave as a pleiotropic hormone. A decade ago, generation of a mouse model devoid of peripheral 5-HT lead to the discovery of a second isoform of the enzyme Tph and also suggested that 5-HT might act as a local regulator in various organs. The objective of this review is to highlight the newly discovered functions played by the monoamine using the Tph1 KO murine model and to outline current findings that led to the discovery of complete serotonergic systems in unexpected organs. Within an organ, both the presence of local Tph enzymatic activity and serotonergic components are of particular importance as they support the view that 5-HT meets the criteria to be qualified as a monoamine with a paracrine/autocrine function.

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Section: ■ Tph1-derived Serotonin In the Gut: What Does It Really Do?mentioning

confidence: 96%

Section: ■ Tph1-derived Serotonin In the Gut: What Does It Really Do?mentioning

confidence: 96%

Life without Peripheral Serotonin: Insights from Tryptophan Hydroxylase 1 Knockout Mice Reveal the Existence of Paracrine/Autocrine Serotonergic Networks

Amireault

Sibon

Côté

2012

ACS Chem. Neurosci.

135

113

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“…[132][133][134] One of the key signaling pathways is via TLR expressed in immune cells of the bowel wall and the neurons of the ENS representing a mechanism for the microbiota to communicate with the CNS. 76 The TLR are pattern recognition receptors detecting lipopolysaccarides (membrane-component of Gram-negative bacteria) and other molecules of microbial origin.…”

Section: Gut-brain Signaling -The Gut Brain Axismentioning

confidence: 99%

Irritable bowel syndrome, the microbiota and the gut-brain axis

Raskov¹,

et al. 2016

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Irritable bowel syndrome is a common functional gastrointestinal disorder and it is now evident that irritable bowel syndrome is a multi-factorial complex of changes in microbiota and immunology. The bidirectional neurohumoral integrated communication between the microbiota and the autonomous nervous system is called the gut-brain-axis, which integrates brain and GI functions, such as gut motility, appetite and weight. The gut-brain-axis has a central function in the perpetuation of irritable bowel syndrome and the microbiota plays a critical role. The purpose of this article is to review recent research concerning the epidemiology of irritable bowel syndrome, influence of microbiota, probiota, gut-brainaxis, and possible treatment modalities on irritable bowel syndrome. The integrated actions and communication between the microbiota and the autonomous nervous system are central players in the perpetuation of IBS symptoms. This signaling pathway is called the GutBrain Axis (GBA). The GBA is a bidirectional neurohumoral communication system that integrates brain and GI functions, such as gut motility, appetite and weightand here the microbiota plays a critical role. 2Changes in gastrointestinal or central nervous system physiology may result in an altered habitat, which again may cause changes in the composition of the microbiota.Disruption of the physiologic symbiotic relationship (eubiosis) between the human host and the microbiota is called dysbiosis and is regarded a basic factor for initiating and maintaining IBS in the majority of patients. Current evidence has suggested that the dysbiosis observed in IBS and the resulting immunological response may drive and perpetuate gastrointestinal symptoms of IBS suggesting that IBS is in fact a disorder of the microbiota and the GBA. It is unclear whether the initiating factor is brain abnormalities that drive the gut changes or if changes in the gut alter brain function through vagal and sympathetic pathways.3,4 The purpose of this article is to review recent research concerning the influence of microbiota and gut-brain-axis on IBS. IBSIt is estimated that approximately 10% of the World population and 15% of the population in the Western World suffer from IBS characterized by a mixture of recurrent abdominal pain, bloating, changing stool consistency such as diarrhea (IBS-D), constipation (IBS-C), or interchanging diarrhea and constipation (mixed-type or IBS-M), mucus secretion, and nausea. 5,6 Community-based data indicate that IBS-M is the most prevalent type followed by IBS-D and IBS-C and that switching among subtypes occurs. Bloating is the most prevalent symptom reported by 96% of patients with IBS of whatever subgroup. 7 In addition to abdominal symptoms, poor sleep, headache, CONTACT Hans Raskov raskov@mail.dk Lundevangsvej 23, DK-2900 Hellerup, Denmark. Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/kgmi.

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“…5,14 Lewy pathology and dopaminergic neuron loss also has been found in the enteric nervous system of many PD patients, particularly the lower gastrointestinal tract, which might be responsible for decreased gastric motility and constipation. 15,16 The inevitability of enteric nervous system pathology in PD has been challenged, however. [17][18][19] These studies show that enteric nervous system Lewy pathology is a frequent, but not necessary concomitant of PD.…”

Section: Introductionmentioning

confidence: 99%