Inhibition of muscarinic receptor-induced proliferation of astroglial cells by ethanol: Mechanisms and implications for the fetal alcohol syndrome

Lucio G. Costa, Marina Guizzetti

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

In utero exposure to ethanol is deleterious to fetal brain development. Children born with the fetal alcohol syndrome (FAS) display a number of abnormalities, the most significant of which are central nervous system (CNS) dysfunctions, such as microencephaly and mental retardation. An interaction of ethanol with glial cells, particularly astrocytes, has been suggested to contribute to the developmental neurotoxicity of this alcohol. At low concentrations (10-100 mM) ethanol inhibits the proliferation of astroglial cells in vitro, particularly when stimulated by acetycholine through muscarinic M3 receptors. Of the several signal transduction pathways activated by these receptors in astrocytes or astrocytoma cells, which are involved in mitogenic signaling, only some (e.g. protein kinase C (PKC) ζ, p70S6 kinase) appear to be targeted by ethanol at the same low concentrations which effectively inhibit proliferation. Inhibition of astroglial proliferation by ethanol may contribute to the microencephaly seen in FAS.

Original languageEnglish (US)
Pages (from-to)685-691
Number of pages7
JournalNeuroToxicology
Volume23
Issue number6
DOIs
StatePublished - Dec 2002
Externally publishedYes

Fingerprint

Fetal Alcohol Spectrum Disorders
Muscarinic Receptors
Ethanol
Alcohols
Cell Proliferation
Astrocytes
Muscarinic M3 Receptors
Signal transduction
Astrocytoma
Neurology
Fetal Development
Neuroglia
Intellectual Disability
Signal Transduction
Brain
Central Nervous System
Inhibition (Psychology)

Keywords

  • Astroglial cells
  • Central nervous system
  • Fetal alcohol syndrome

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neuroscience(all)
  • Toxicology

Cite this

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title = "Inhibition of muscarinic receptor-induced proliferation of astroglial cells by ethanol: Mechanisms and implications for the fetal alcohol syndrome",
abstract = "In utero exposure to ethanol is deleterious to fetal brain development. Children born with the fetal alcohol syndrome (FAS) display a number of abnormalities, the most significant of which are central nervous system (CNS) dysfunctions, such as microencephaly and mental retardation. An interaction of ethanol with glial cells, particularly astrocytes, has been suggested to contribute to the developmental neurotoxicity of this alcohol. At low concentrations (10-100 mM) ethanol inhibits the proliferation of astroglial cells in vitro, particularly when stimulated by acetycholine through muscarinic M3 receptors. Of the several signal transduction pathways activated by these receptors in astrocytes or astrocytoma cells, which are involved in mitogenic signaling, only some (e.g. protein kinase C (PKC) ζ, p70S6 kinase) appear to be targeted by ethanol at the same low concentrations which effectively inhibit proliferation. Inhibition of astroglial proliferation by ethanol may contribute to the microencephaly seen in FAS.",
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