title: Prenatal Ethanol Exposure Up-Regulates the Cholesterol Transporters ATP-Binding Cassette A1 and G1 and Reduces Cholesterol Levels in the Developing Rat Brain.
abstract: OBJECTIVE
  Cholesterol plays a pivotal role in many aspects of brain development; reduced cholesterol levels during brain development, as a consequence of genetic defects in cholesterol biosynthesis, leads to severe brain damage, including microcephaly and mental retardation, both of which are also hallmarks of the fetal alcohol syndrome. We had previously shown that ethanol up-regulates the levels of two cholesterol transporters, ABCA1 (ATP binding cassette-A1) and ABCG1, leading to increased cholesterol efflux and decreased cholesterol content in astrocytes in vitro. In the present study we investigated whether similar effects could be seen in vivo.
  
  
  METHODS
  Pregnant Sprague-Dawley rats were fed liquid diets containing 36% of the calories from ethanol from gestational day (GD) 6 to GD 21. A pair-fed control groups and an ad libitum control group were included in the study. ABCA1 and ABCG1 protein expression and cholesterol and phospholipid levels were measured in the neocortex of female and male fetuses at GD 21.
  
  
  RESULTS
  Body weights were decreased in female fetuses as a consequence of ethanol treatments. ABCA1 and ABCG1 protein levels were increased, and cholesterol levels were decreased, in the neocortex of ethanol-exposed female, but not male, fetuses. Levels of phospholipids were unchanged. Control female fetuses fed ad libitum displayed an up-regulation of ABCA1 and a decrease in cholesterol content compared with pair-fed controls, suggesting that a compensatory up-regulation of cholesterol levels may occur during food restriction.
  
  
  CONCLUSIONS
  Maternal ethanol consumption may affect fetal brain development by increasing cholesterol transporters' expression and reducing brain cholesterol levels.
authors: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
authors: Chunyan
authors: C
authors: Zhou
authors: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
authors: Jing
authors: J
authors: Chen
authors: Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA Jesse Brown VA Medical Center, Chicago, IL, USA.
authors: Xiaolu
authors: X
authors: Zhang
authors: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA Department of Neuroscience, University of Parma, Parma, Italy.
authors: Lucio G
authors: LG
authors: Costa
authors: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA Jesse Brown VA Medical Center, Chicago, IL, USA mguizzetti@psych.uic.edu.
authors: Marina
authors: M
authors: Guizzetti
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000032:analysis / Q000378:metabolism*; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000196:embryology; D001923:Brain Chemistry / Q000187:drug effects*; D002784:Cholesterol / Q000032:analysis*; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D008297:Male; D010743:Phospholipids / Q000032:analysis; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D002784:Cholesterol; D000431:Ethanol; D010743:Phospholipids; C577834:Abca1 protein, rat; C559724:Abcg1 protein, rat