Essential Roles of Enteric Neuronal Serotonin in Gastrointestinal Motility and the Development/Survival of Enteric Dopaminergic Neurons
- 15 June 2011
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 31 (24), 8998-9009
- https://doi.org/10.1523/jneurosci.6684-10.2011
Abstract
The gut contains a large 5-HT pool in enterochromaffin (EC) cells and a smaller 5-HT pool in the enteric nervous system (ENS). During development, enteric neurons are generated asynchronously. We tested hypotheses that serotonergic neurons, which arise early, affect development/survival of later-born dopaminergic, GABAergic, nitrergic, and calcitonin gene-related peptide-expressing neurons and are essential for gastrointestinal motility. 5-HT biosynthesis depends on tryptophan hydroxylase 1 (TPH1) in EC cells and on TPH2 in neurons; therefore, mice lacking TPH1 and/or TPH2 distinguish EC-derived from neuronal 5-HT. Deletion of TPH2, but not TPH1, decreased myenteric neuronal density and proportions of dopaminergic and GABAergic neurons but did not affect the extrinsic sympathetic innervation of the gut; intestinal transit slowed in mice lacking TPH2 mice, but gastric emptying accelerated. Isolated enteric crest-derived cells (ENCDCs) expressed the serotonin reuptake transporter (SERT) and 15 subtypes of 5-HT receptor. Addition of 5-HT to cultures of isolated ENCDCs promoted total and dopaminergic neuronal development. Rings of SERT-immunoreactive terminal axons surrounded myenteric dopaminergic neurons and SERT knock-out increased intestinal levels of dopamine metabolites, implying that enteric dopaminergic neurons receive a serotonergic innervation. Observations suggest that constitutive gastrointestinal motility depends more on neuronal than EC cell serotonin; moreover, serotonergic neurons promote development/survival of some classes of late-born enteric neurons, including dopaminergic neurons, which appear to innervate and activate in the adult ENS.Keywords
This publication has 74 references indexed in Scilit:
- Colonic elongation inhibits pellet propulsion and migrating motor complexes in the murine large bowelJournal Of Physiology-London, 2010
- Critical role of 5-HT1A, 5-HT3, and 5-HT7 receptor subtypes in the initiation, generation, and propagation of the murine colonic migrating motor complexAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2010
- 5-HT4Receptor-Mediated Neuroprotection and Neurogenesis in the Enteric Nervous System of Adult MiceJournal of Neuroscience, 2009
- Enteric serotonergic neurones … finally!Journal Of Physiology-London, 2009
- Strain‐specific genetics, anatomy and function of enteric neural serotonergic pathways in inbred miceJournal Of Physiology-London, 2009
- Lrp5 Controls Bone Formation by Inhibiting Serotonin Synthesis in the DuodenumCell, 2008
- Genetic Disruption of Both Tryptophan Hydroxylase Genes Dramatically Reduces Serotonin and Affects Behavior in Models Sensitive to AntidepressantsPLOS ONE, 2008
- Bone morphogenetic protein regulation of enteric neuronal phenotypic diversity: Relationship to timing of cell cycle exitJournal of Comparative Neurology, 2008
- High Mucosal Serotonin Availability in Neonatal Guinea Pig Ileum Is Associated With Low Serotonin Transporter ExpressionGastroenterology, 2007
- An ultrastructural analysis of the developing enteric nervous system of the guinea-pig small intestineJournal of Neurocytology, 1981