Ethanol consumption during early pregnancy alters the disposition of tangentially migrating GABAergic interneurons in the fetal cortex

Verginia Cuzon Carlson, Pamela W L Yeh, Yuchio Yanagawa, Kunihiko Obata, Hermes H. Yeh

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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 GABAA receptor function.

Original languageEnglish (US)
Pages (from-to)1854-1864
Number of pages11
JournalJournal of Neuroscience
Volume28
Issue number8
DOIs
StatePublished - Feb 20 2008
Externally publishedYes

Fingerprint

Interneurons
Ethanol
Pregnancy
Median Eminence
gamma-Aminobutyric Acid
Fetal Alcohol Spectrum Disorders
Coculture Techniques
Embryonic Structures
Telencephalon
Intrinsic Factor
GABA-A Receptors
Fetal Blood
Alcohol Drinking
Embryonic Development
Mothers
Brain

Keywords

  • Ambient GABA
  • Fetal alcohol syndrome
  • GABA receptor
  • GFP+/MGE
  • Medial ganglionic eminence
  • Telencephalic slice culture

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ethanol consumption during early pregnancy alters the disposition of tangentially migrating GABAergic interneurons in the fetal cortex. / Cuzon Carlson, Verginia; Yeh, Pamela W L; Yanagawa, Yuchio; Obata, Kunihiko; Yeh, Hermes H.

In: Journal of Neuroscience, Vol. 28, No. 8, 20.02.2008, p. 1854-1864.

Research output: Contribution to journalArticle

Cuzon Carlson, Verginia ; Yeh, Pamela W L ; Yanagawa, Yuchio ; Obata, Kunihiko ; Yeh, Hermes H. / Ethanol consumption during early pregnancy alters the disposition of tangentially migrating GABAergic interneurons in the fetal cortex. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 8. pp. 1854-1864.
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