PMID- 25081040 OWN - NLM STAT- MEDLINE DCOM- 20160818 LR - 20230411 IS - 1464-3502 (Electronic) IS - 0735-0414 (Print) IS - 0735-0414 (Linking) VI - 49 IP - 6 DP - 2014 Nov TI - Prenatal Ethanol Exposure Up-Regulates the Cholesterol Transporters ATP-Binding Cassette A1 and G1 and Reduces Cholesterol Levels in the Developing Rat Brain. PG - 626-34 LID - 10.1093/alcalc/agu049 [doi] AB - AIMS: 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. CONCLUSION: Maternal ethanol consumption may affect fetal brain development by increasing cholesterol transporters' expression and reducing brain cholesterol levels. CI - (c) The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved. FAU - Zhou, Chunyan AU - Zhou C AD - Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA. FAU - Chen, Jing AU - Chen J AD - Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA. FAU - Zhang, Xiaolu AU - Zhang X AD - Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA Jesse Brown VA Medical Center, Chicago, IL, USA. FAU - Costa, Lucio G AU - Costa LG AD - Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA Department of Neuroscience, University of Parma, Parma, Italy. FAU - Guizzetti, Marina AU - Guizzetti M AD - 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. LA - eng GR - R01 AA017180/AA/NIAAA NIH HHS/United States GR - R21 AA021876/AA/NIAAA NIH HHS/United States GR - AA017180/AA/NIAAA NIH HHS/United States GR - AA021876/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140731 PL - England TA - Alcohol Alcohol JT - Alcohol and alcoholism (Oxford, Oxfordshire) JID - 8310684 RN - 0 (ABCA1 protein, rat) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Abcg1 protein, rat) RN - 0 (Phospholipids) RN - 3K9958V90M (Ethanol) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - ATP Binding Cassette Transporter 1/analysis/*metabolism MH - ATP Binding Cassette Transporter, Subfamily G, Member 1 MH - ATP-Binding Cassette Transporters/analysis/*metabolism MH - Animals MH - Blotting, Western MH - Brain/drug effects/embryology MH - Brain Chemistry/*drug effects MH - Cholesterol/*analysis MH - Ethanol/*adverse effects MH - Female MH - Male MH - Phospholipids/analysis MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*metabolism MH - Rats MH - Rats, Sprague-Dawley PMC - PMC4834908 EDAT- 2014/08/02 06:00 MHDA- 2016/08/19 06:00 PMCR- 2015/11/01 CRDT- 2014/08/02 06:00 PHST- 2013/10/15 00:00 [received] PHST- 2014/06/17 00:00 [accepted] PHST- 2014/08/02 06:00 [entrez] PHST- 2014/08/02 06:00 [pubmed] PHST- 2016/08/19 06:00 [medline] PHST- 2015/11/01 00:00 [pmc-release] AID - agu049 [pii] AID - 10.1093/alcalc/agu049 [doi] PST - ppublish SO - Alcohol Alcohol. 2014 Nov;49(6):626-34. doi: 10.1093/alcalc/agu049. Epub 2014 Jul 31.