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


Journal article


Zhishan Li, A. Chalazonitis, Yung-yu Huang, J. Mann, K. Margolis, Q. Yang, Dolly O. Kim, F. Côté, J. Mallet, M. Gershon
Journal of Neuroscience, 2011

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APA   Click to copy
Li, Z., Chalazonitis, A., Huang, Y.-yu, Mann, J., Margolis, K., Yang, Q., … Gershon, M. (2011). Essential Roles of Enteric Neuronal Serotonin in Gastrointestinal Motility and the Development/Survival of Enteric Dopaminergic Neurons. Journal of Neuroscience.


Chicago/Turabian   Click to copy
Li, Zhishan, A. Chalazonitis, Yung-yu Huang, J. Mann, K. Margolis, Q. Yang, Dolly O. Kim, F. Côté, J. Mallet, and M. Gershon. “Essential Roles of Enteric Neuronal Serotonin in Gastrointestinal Motility and the Development/Survival of Enteric Dopaminergic Neurons.” Journal of Neuroscience (2011).


MLA   Click to copy
Li, Zhishan, et al. “Essential Roles of Enteric Neuronal Serotonin in Gastrointestinal Motility and the Development/Survival of Enteric Dopaminergic Neurons.” Journal of Neuroscience, 2011.


BibTeX   Click to copy

@article{zhishan2011a,
  title = {Essential Roles of Enteric Neuronal Serotonin in Gastrointestinal Motility and the Development/Survival of Enteric Dopaminergic Neurons},
  year = {2011},
  journal = {Journal of Neuroscience},
  author = {Li, Zhishan and Chalazonitis, A. and Huang, Yung-yu and Mann, J. and Margolis, K. and Yang, Q. and Kim, Dolly O. and Côté, F. and Mallet, J. and Gershon, M.}
}

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.