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首页> 外文期刊>Alcohol >Maternal choline supplementation in a sheep model of first trimester binge alcohol fails to protect against brain volume reductions in peripubertal lambs
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Maternal choline supplementation in a sheep model of first trimester binge alcohol fails to protect against brain volume reductions in peripubertal lambs

机译：母胆碱补充在孕期泪液的绵羊模型中未能防止危险羔羊的脑体积减少

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Fetal alcohol spectrum disorder (FASD) is a leading potentially preventable birth defect. Poor nutrition may contribute to adverse developmental outcomes of prenatal alcohol exposure, and supplementation of essential micronutrients such as choline has shown benefit in rodent models. The sheep model of first trimester binge alcohol exposure was used in this study to model the dose of maternal choline supplementation used in an ongoing prospective clinical trial involving pregnancies at risk for FASD. Primary outcome measures including volumetrics of the whole brain, cerebellum, and pituitary derived from magnetic resonance imaging (MRI) in 6-month-old lambs, testing the hypothesis that alcohol-exposed lambs would have brain volume reductions that would be ameliorated by maternal choline supplementation. Pregnant sheep were randomly assigned to one of five groups - heavy binge alcohol (HBA; 2.5 g/kg/treatment ethanol), heavy binge alcohol plus choline supplementation (HBC; 2.5 g/kg/treatment ethanol and 10 mg/kg/day choline), saline control (SC), saline control plus choline supplementation (SCC; 10 mg/kg/day choline), and normal control (NC). Ewes were given intravenous alcohol (HBA, HBC; mean peak BACs of similar to 280 mg/dL) or saline (SC, SCC) on three consecutive days per week from gestation day (GD) 4-41; choline was administered on GD 4-148. MRI scans of lamb brains were performed postnatally on day 182. Lambs from both alcohol groups (with or without choline) showed significant reductions in total brain volume; cerebellar and pituitary volumes were not significantly affected. This is the first report of MRI-derived volumetric brain reductions in a sheep model of FASD following binge-like alcohol exposure during the first trimester. These results also indicate that maternal choline supplementation comparable to doses in human studies fails to prevent brain volume reductions typically induced by first-trimester binge alcohol exposure. Future analyses will assess behavioral outcomes along with regional brain and neurohistological measures. (C) 2016 Elsevier Inc. All rights reserved.
机译：胎儿酒精谱系障碍（FASD）是一个领先的潜在可预防的出生缺陷。营养不良可能导致产前酒精暴露的不利发育结果，补充必要的微量营养素如胆碱在啮齿动物模型中表现出受益。本研究中使用了第一个妊娠酒精暴露的绵羊模型，以模拟涉及FASD风险危险的持续前瞻性临床试验中使用的母体胆碱补充剂的剂量。在6个月大的羊羔中，在6个月大的羊羔中源于磁共振成像（MRI）的全脑，小脑和垂体垂体的主要结果措施，测试了酒精暴露的羊羔的假设，该假设将具有母胆碱可以改善的脑体积减少补充。将孕妇随机分配到五组 - 重质醇（HBA; 2.5g / kg /处理乙醇）中的一种，重泪液加上胆碱补充剂（HBC; 2.5g / kg / proppation乙醇和10mg / kg / day choline ），盐水控制（SC），盐水控制加胆碱补充（SCC; 10毫克/千克/天胆碱）和正常对照（NC）。从妊娠日（GD）4-41（GD）4-41，每周三天，eWES被静脉内醇（HBA，HBC;类似于280mg / dl）或盐水（SC，SCC）的盐水（SC，SCC）;胆碱在GD 4-148上施用。在第182天的第182天，早期进行羊肉扫描的MRI扫描。来自醇组（有或没有胆碱）的羔羊显示出总脑体积的显着降低;小脑和垂体体积没有显着影响。这是MRI衍生体积脑减少的第一个报告，在妊娠早期在麦芽糖般的酒精暴露之后FASD的绵羊模型。这些结果还表明，与人类研究中的剂量相当的母体胆碱补充不能防止通常通过先妊娠酒精暴露诱导的脑体积减少。未来的分析将评估行为结果以及区域大脑和神经外杂志的措施。 （c）2016年Elsevier Inc.保留所有权利。

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