| Ethanol consumption during early pregnancy alters the disposition of tangentially migrating GABAergic interneurons in the fetal cortex. | |
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MedLine Citation:
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PMID: 18287502 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Consumption of alcohol (ethanol) during pregnancy can lead to developmental defects in the offspring, the most devastating being the constellation of symptoms collectively referred to as fetal alcohol syndrome (FAS). In the brain, a hallmark of FAS is abnormal cerebral cortical morphology consistent with insult during corticogenesis. Here, we report that exposure to a relatively low level of ethanol in utero (average maternal and fetal blood alcohol level of 25 mg/dl) promotes premature tangential migration into the cortical anlage of primordial GABAergic interneurons, including those originating in the medial ganglionic eminence (MGE). This ethanol-induced effect was evident in vivo at embryonic day 14.5 (E14.5) in GAD67 knock-in and BAC-Lhx6 embryos, as well as in vitro in isotypic telencephalic slice cocultures obtained from E14.5 embryos exposed to ethanol in utero. Analysis of heterotypic cocultures indicated that both cell-intrinsic and -extrinsic factors contribute to the aberrant migratory profile of MGE-derived cells. In this light, we provide evidence for an interaction between ethanol exposure in utero and the embryonic GABAergic system. Exposure to ethanol in utero elevated the ambient level of GABA and increased the sensitivity to GABA of MGE-derived cells. Our results uncovered for the first time an effect of ethanol consumption during pregnancy on the embryonic development of GABAergic cortical interneurons. We propose that ethanol exerts its effect on the tangential migration of GABAergic interneurons extrinsically by modulating extracellular levels of GABA and intrinsically by altering GABA(A) receptor function. |
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Authors:
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Verginia C Cuzon; Pamela W L Yeh; Yuchio Yanagawa; Kunihiko Obata; Hermes H Yeh |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 28 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2008-02-21 Completed Date: 2008-03-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 1854-64 Citation Subset: IM |
Affiliation:
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Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alcohol Drinking
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adverse effects Animals Cell Movement / drug effects*, physiology Cerebral Cortex / cytology, drug effects*, embryology* Coculture Techniques Ethanol / administration & dosage*, toxicity Female Fetus Interneurons / cytology, drug effects*, physiology Mice Mice, Inbred C57BL Mice, Transgenic Pregnancy Time Factors gamma-Aminobutyric Acid / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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F31 AA014698/AA/NIAAA NIH HHS; R01 MH069826/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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56-12-2/gamma-Aminobutyric Acid; 64-17-5/Ethanol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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