Prenatal Ethanol Exposure Up-Regulates the Cholesterol Transporters ATP-Binding Cassette A1 and G1 and Reduces Cholesterol Levels in the Developing Rat Brain.
Prenatal Ethanol Exposure Up-Regulates the Cholesterol Transporters ATP-Binding Cassette A1 and G1 and Reduces Cholesterol Levels in the Developing Rat Brain.
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产前乙醇暴露上调胆固醇转运蛋白 ATP 结合盒 A1 和 G1，并降低发育中的大鼠大脑中的胆固醇水平。
DOI：
10.1093/alcalc/agu049
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Guizzetti,Marina
中科院分区：
文献类型：
--
作者：
Zhou,Chunyan;Chen,Jing;Zhang,Xiaolu;Costa,LucioG;Guizzetti,Marina
AimsCholesterol 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 astrocytesin vitro. In the present study we investigated whether similar effects could be seenin vivo.MethodsPregnant 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 anad libitumcontrol 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.ResultsBody 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 fedad libitumdisplayed 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.ConclusionMaternal ethanol consumption may affect fetal brain development by increasing cholesterol transporters’ expression and reducing brain cholesterol levels.
