Document Detail

Fetal, maternal, and placental sources of serotonin and new implications for developmental programming of the brain.
MedLine Citation:
PMID:  22001683     Owner:  NLM     Status:  MEDLINE    
In addition to its role in neurotransmission, embryonic serotonin (5-HT) has been implicated in the regulation of neurodevelopmental processes. For example, we recently showed that a subset of 5-HT1-receptors expressed in the fetal forebrain mediate a serotonergic modulation of thalamocortical axons response to axon guidance cues, both in vitro and in vivo. This influence of 5-HT signaling on fetal brain wiring raised important questions regarding the source of the ligand during pregnancy. Until recently, it was thought that 5-HT sources impacting brain development arose from maternal transport to the fetus, or from raphe neurons in the brainstem of the fetus. Using genetic mouse models, we uncovered previously unknown differences in 5-HT accumulation between the fore- and hindbrain during early and late fetal stages, through an exogenous source of 5-HT. Using additional genetic strategies, a new technology for studying placental biology ex vivo, and direct manipulation of placental neosynthesis, we investigated the nature of this exogenous source and uncovered a placental 5-HT synthetic pathway from a maternal tryptophan precursor, in both mice and humans. These results implicate a new, direct role for placental metabolic pathways in modulating fetal brain development and suggest an important role for maternal-placental-fetal interactions and 5-HT in the fetal programming of adult mental disorders.
A Bonnin; P Levitt
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2011-10-08
Journal Detail:
Title:  Neuroscience     Volume:  197     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-07     Completed Date:  2012-02-27     Revised Date:  2014-09-09    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
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MeSH Terms
Brain / embryology*
Fetal Development / physiology*
Fetus / metabolism*
Neurogenesis / physiology*
Placenta / metabolism*
Serotonin / metabolism*
Grant Support
1P50MH078280A1/MH/NIMH NIH HHS; 5R21HD065287/HD/NICHD NIH HHS; P50 MH078028/MH/NIMH NIH HHS; P50 MH078028-05/MH/NIMH NIH HHS; R21 HD065287/HD/NICHD NIH HHS; R21 HD065287-02/HD/NICHD NIH HHS
Reg. No./Substance:

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