Essential roles of enteric neuronal serotonin in gastrointestinal motility and the development/survival of enteric dopaminergic neurons. Li, Z., Chalazonitis, A., Huang, Y., Mann, J. J., Margolis, K. G., Yang, Q. M., Kim, D. O., Côté, F., Mallet, J., & Gershon, M. D. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 31(24):8998–9009, June, 2011.
doi  abstract   bibtex   
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.
@article{li_essential_2011,
	title = {Essential roles of enteric neuronal serotonin in gastrointestinal motility and the development/survival of enteric dopaminergic neurons},
	volume = {31},
	issn = {1529-2401},
	doi = {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.},
	language = {eng},
	number = {24},
	journal = {The Journal of Neuroscience: The Official Journal of the Society for Neuroscience},
	author = {Li, Zhishan and Chalazonitis, Alcmène and Huang, Yung-Yu and Mann, J. John and Margolis, Kara Gross and Yang, Qi Melissa and Kim, Dolly O. and Côté, Francine and Mallet, Jacques and Gershon, Michael D.},
	month = jun,
	year = {2011},
	pmid = {21677183},
	pmcid = {PMC4442094},
	keywords = {Animals, Calcitonin Gene-Related Peptide, Dopamine, ELAV Proteins, ELAV-Like Protein 3, Embryo, Mammalian, Enteric Nervous System, Enzyme Inhibitors, Gastric Emptying, Gastrointestinal Motility, Gene Expression Regulation, Developmental, Homovanillic Acid, In Vitro Techniques, Intestine, Small, Mice, Mice, Inbred C57BL, Myenteric Plexus, Neurons, Nitric Oxide Synthase Type I, Serotonin, Serotonin Plasma Membrane Transport Proteins, Tryptophan Hydroxylase, Tyrosine 3-Monooxygenase, gamma-Aminobutyric Acid},
	pages = {8998--9009},
}

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