Synergy of nutrients and the prevention of Fetal Alcohol Spectrum Disorders (FASD): effects on brain development and function in a rat model.

营养素的协同作用和预防胎儿酒精谱系障碍 (FASD)：对大鼠模型大脑发育和功能的影响。

• 批准号: 10256641
• 负责人: Carol L Cheatham
• 金额: $ 18.47万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-10 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10256641
• 关键词: Adverse effects; Affect; Alcohols; Analysis of Variance; Animal Model; Animals; Appearance; Attenuated; Behavioral; Bilateral; Bioavailable; Biological Assay; Brain; Canada; Child; Choline; Client; Clinic; Cognitive; Consumption; Data; Development; Diagnosis; Diet; Dietary Intervention; Docosahexaenoic Acids; Ear; Eye; Face; Female; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal alcohol effects; Fetus; Food; Goals; High Pressure Liquid Chromatography; Hippocampus (Brain); Human Milk; Infant Development; Intervention; Lecithin; Length; Liquid substance; Liver; Marketing; Measures; Medial; Modeling; National Institute of Diabetes and Digestive and Kidney Diseases; Neurologic Effect; Neurons; Nutrient; Obesity; Outcome; Phosphatidylserines; Phospholipids; Prefrontal Cortex; Pregnancy; Pregnant Women; Prevalence; Prevention; Proteins; Rattus; Reporting; Research; Research Design; Risk; Sampling; Scientist; Series; Short-Term Memory; Structure; Synapses; Synapsins; Testing; Therapeutic; Time; Training; Translating; Translations; United States; Uridine; Western Blotting; Woman; Work; alcohol abstinence; alcohol consumption during pregnancy; alcohol effect; alcohol exposure; attenuation; autism spectrum disorder; brain tissue; chicken egg; choline supplementation; cognitive ability; cognitive development; design; egg; executive function; experimental study; fetal; fetus at risk; flexibility; frontal lobe; improved; improved outcome; male; memory process; morris water maze; neurobehavioral; neuron development; novel strategies; nutrition; offspring; postnatal; postsynaptic; pre-clinical; preclinical study; pregnant; prenatal; prevent; programs; prophylactic; pup; spatial memory; success; synergism; unborn child

7. PROJECT SUMMARY Despite prolific marketing campaigns explaining the dangers of consuming alcohol during pregnancy, the prevalence of Fetal Alcohol Spectrum Disorders (FASD) in the United States is 2-5%, which is higher than the rate of Autism Spectrum Disorders. Whether it is because a woman was unaware of the pregnancy, ignorant of the risk, dismissing of the risk, or unable to abstain, women do drink during pregnancy, and therefore, it is imperative that we find a way to prevent FASD. Optimal nutrition is essential for the developing fetal brain and is generally lacking in active drinkers. One nutrient, choline, has been shown to ameliorate the effects of fetal alcohol exposure in animal models. Translation to the clinic shows promise, but scientists report mixed or limited results. Importantly, with each successive pregnancy, DHA stores become depleted, and with each successive pregnancy, the risk of FASD increases. Thus, maternal DHA deficiency may be implicated in FASD. Indeed, DHA and choline work together to deliver DHA to the brain where it supports brain function. This synergistic activity is further enhanced by the addition of uridine. To explore this synergy hypothesis, we will test a natural therapeutic prenatal prophylactic that contains DHA, choline, and uridine and is easily translatable to the clinic - the chicken egg - in a preclinical study. Our central hypothesis is that the synergistic activity of DHA, choline, and uridine in egg will mitigate the effects of fetal alcohol exposure on the developing hippocampus and frontal lobes. Importantly, these experiments will be the first in a program of research designed to establish the mechanisms through which synergistic nutrients ameliorate the effect of prenatal alcohol exposure on fetal brain development. In the proposed work, pregnant dams will be fed experimental diets from gestational day GD5 to GD20 in a 2 (Prenatal Exposure: Ethanol, Pair-fed Control) X 5 (Diet: Egg, Choline, DHA, Uridine, Unsupplemented) design. Subsequent pups will be observed for early physical (ear unfurling, eye opening, appearance of fur) and behavioral (e.g., self-righting, cliff avoidance) development in a series of tests. Groups will be compared on day of success in a Chi-square analysis for discrete variables. Starting on PD45, random subsets (one male and one female per litter) will be trained and tested on a classic Morris Water Maze spatial and working memory tests. Data will be subjected to analyses of variance between groups. Brain tissue will be assayed for phospholipid and uridine content and synaptic proteins will be quantified with immunoblots. We predict that the ethanol effects will be reduced in the egg-supplemented groups compared to the non-egg groups. The results of this experiment will inform interventions for pregnant women who are unable to abstain from consuming alcohol during pregnancy and their at-risk fetuses. If our preclinical work shows promise, we will translate the work to the clinic, working with support programs in the US and Canada to provide the food to their clients and thereby, improve the outcomes and the subsequent lives of their unborn children.

7。项目摘要 尽管多产的营销活动解释了怀孕期间饮酒的危险，但 美国胎儿酒精谱系障碍（FASD）的患病率为2-5％，高于 自闭症谱系障碍率。是否是因为女人不知道怀孕， 一无所知的风险，驳回风险或无法避免的风险，妇女在怀孕期间确实喝酒，并且 因此，我们必须找到一种防止FASD的方法。 最佳营养对于发育中的胎儿大脑至关重要，通常缺乏活跃的饮酒者。 已经证明一种营养素可以改善动物模型中胎儿酒精暴露的影响。 转化为诊所表现出希望，但科学家报告了混合或有限的结果。重要的是，每个 连续怀孕，DHA商店耗尽，每次连续怀孕，FASD的风险 增加。因此，母体DHA缺乏症可能与FASD有关。确实，DHA和胆碱一起工作 将DHA运送到支持大脑功能的大脑。这种协同活动进一步增强了 加入尿苷。为了探索这种协同假设，我们将测试自然治疗产前预防性 其中包含DHA，胆碱和尿苷，很容易翻译成临床上的诊所 - 鸡蛋 学习。我们的中心假设是DHA，胆碱和尿中尿中的协同活性将减轻 胎儿酒精暴露对发展中的海马和额叶叶的影响。重要的是，这些 实验将是旨在建立机制的研究计划中的第一个。 协同营养可以改善产前酒精暴露对胎儿脑发育的影响。 在拟议的工作中，孕妇的大坝将得到实验性饮食，从妊娠日GD5到GD20 在2（产前暴露：乙醇，配对对照）x 5（饮食：鸡蛋，胆碱，DHA，尿苷，未补充） 设计。将观察到随后的幼崽的早期物理（耳朵伸开，睁眼，毛皮外观） 和行为（例如，自我impling，避免悬崖）在一系列测试中的发展。将比较小组 在成功分析的离散变量的卡方分析中。从PD45开始，随机子集（一个男性 每窝中的一名女性）将在经典的莫里斯水迷宫空间和工作中进行训练和测试 内存测试。数据将经过组之间的差异分析。将分析脑组织 磷脂和尿苷含量以及突触蛋白将用免疫印迹进行定量。我们预测 与非蛋群相比，补充卵子组的乙醇效应将降低。 该实验的结果将为无法弃权的孕妇提供干预措施 从怀孕期间饮酒及其高危胎儿。如果我们的临床前工作表现出希望，我们 将把工作转化为诊所，与美国和加拿大的支持计划一起提供食物 他们的客户，从而改善未出生的孩子的结果和后续生活。