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首页> 外文期刊>Alcohol >Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure
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Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure

机译：产后胆碱补充选择性地衰减与发育酒精暴露有关的海马微小RNA改变

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Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol's developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation. To determine whether choline supplementation alters ethanol's long-lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol from postnatal days (PD) 4-9 via intubation; controls received sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline vehicle subcutaneously (s.c.) from PD 4-21. On PD 22, subjects were sacrificed, and RNA was isolated from the hippocampus. MiRNA expression was assessed with TagMan Human MicroRNA Panel Low-Density Arrays. Ethanol significantly increased miRNA expression variance, an effect that was attenuated with choline supplementation. Cluster analysis of stably expressed miRNAs that exceeded an ANOVA p < 0.05 criterion indicated that for both male and female offspring, control and ethanol-exposed groups were most dissimilar from each other, with choline-supplemented groups in between. MiRNAs that expressed an average 2-fold change due to ethanol exposure were further analyzed to identify which ethanol-sensitive miRNAs were protected by choline supplementation. We found that at a false discovery rate (FDR)-adjusted criterion of p < 0.05, miR-200c was induced by ethanol exposure and that choline prevented this effect. Collectively, our data show that choline supplementation can normalize disturbances in miRNA expression following developmental alcohol exposure and can protect specific miRNAs from induction by ethanol. These findings have important implications for the mechanisms by which choline may serve as a potential treatment for FASD. (C) 2017 Elsevier Inc. All rights reserved.
机译：产前酒精暴露可导致一系列物理，神经病理和行为改变，集体称为胎儿醇谱紊乱（FASD）。我们已经表明，补充营养胆碱的补充降低了海马依赖行为中发育醇相关缺陷的严重程度，并使海马胆碱能发育和DNA甲基化图案正常化。还可以通过改变作为基因翻译的负调节剂的MicroRNAs（miRNA）来介导醇的发育效果。为了确定胆碱补充是否改变了乙醇对miRNA的持久影响，Sprague-Dawley大鼠通过插管从后期（Pd）4-9暴露于5.25g / kg /天乙醇;控件接受了假插管。将受试者用氯化胆碱（100mg / kg /天）或盐水载体皮下从PD 4-21进行处理。在PD 22上，处死受试者，并从海马中分离RNA。用标记人类MicroRNA面板低密度阵列评估miRNA表达。乙醇显着提高miRNA表达方差，胆碱补充剂的效果。超过ANOVA P <0.05标准的稳定表达miRNA的聚类分析表明，对于雄性和女性后代，对照和乙醇暴露的基团彼此最异常，其中胆碱补充基团。进一步分析表达由于乙醇暴露引起的平均2倍变化的miRNA，以确定哪种乙醇敏感的miRNA受胆碱补充剂的保护。我们发现，对于P <0.05的P <0.05的假发现率（FDR），通过乙醇暴露诱导miR-200c，并且胆碱预防了这种效果。统称，我们的数据显示，在发育酒精暴露后，胆碱补充可以使miRNA表达中的干扰正常化，并且可以保护特异性miRNA免受乙醇的诱导。这些发现对胆碱可以作为FASD潜在治疗的机制具有重要意义。 （c）2017年Elsevier Inc.保留所有权利。

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