Cholesterol homeostasis in the developing brain: A possible new target for ethanol

Marina Guizzetti, L. G. Costa

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Cholesterol is an essential component of cell membranes and plays an important role in signal transduction. This brief overview presents evidence from the literature that ethanol may affect cholesterol homeostasis and that, in the developing brain, this may be involved in its developmental neurotoxicity. The effects caused by inborn errors of cholesterol synthesis and by in utero ethanol exposure present several similarities in humans (eg, Smith-Lemli-Opitz syndrome and fetal alcohol syndrome), as well as in animal models. Ethanol has a cholesterol-reducing effect on the cardiovascular system, and a protective effect against Alzheimer's disease, whose pathogenesis has been linked to altered cholesterol homeostasis in the brain. In vitro, ethanol affects several functions that are mediated by cholesterol and important for brain development, such as glial cell proliferation, synaptogenesis, neuronal survival and neurite outgrowth. The brain contains high levels of cholesterol, mostly synthesized in situ. Astrocytes produce large amounts of cholesterol that can be released by these cells and utilized by neurons to form synapses. Ethanol upregulates the cholesterol transporter ATP binding cassette A1 and cholesterol efflux from primary astrocyte cultures without affecting cholesterol synthesis.

Original languageEnglish (US)
Pages (from-to)355-360
Number of pages6
JournalHuman and Experimental Toxicology
Volume26
Issue number4
DOIs
StatePublished - Apr 2007

Keywords

  • Astrocytes
  • Cholesterol
  • Ethanol
  • Fetal alcohol syndrome

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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