Nutrient combination to mitigate Fetal Alcohol Spectrum Disorder

缓解胎儿酒精谱系障碍的营养组合

• 批准号: 9913640
• 负责人: Sandra M Mooney
• 金额: $ 15.55万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9913640
• 关键词: Address; Adolescence; Adverse effects; Affect; Aging; Alcohols; Animals; Attentional deficit; Attenuated; Behavior; Behavioral; Bilateral; Blood alcohol level measurement; Brain; Child; Childhood; Choline; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Conceptions; Consumption; Control Animal; Data; Dendritic Spines; Development; Diagnosis; Docosahexaenoic Acids; Dose; Ethanol; Experimental Designs; Exposure to; Face; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal alcohol effects; Fetus; Hippocampus (Brain); Human; Human Milk; Hyperactive behavior; Impairment; Infant Development; Intervention; Learning; Liver; Memory; Methods; Modeling; Morbidity - disease rate; Neuroanatomy; Nutrient; Outcome; Performance; Prefrontal Cortex; Pregnancy; Problem Solving; Proteins; Psyche structure; Rattus; Rodent Model; Scientist; Sensory; Short-Term Memory; Social Behavior; Structure; Supplementation; Synapses; Testing; Therapeutic Intervention; Training; United States; Uridine; Western Blotting; Woman; Work; alcohol effect; alcohol exposure; animal data; behavior change; choline supplementation; clinically relevant; cognitive ability; cognitive development; cognitive function; cognitive performance; cognitive training; executive function; experimental study; fetal; flexibility; frontal lobe; improved; innovation; memory process; neuron development; nutrition; offspring; parent grant; postnatal; prenatal; protein expression; pup; synergism; young adult

Abstract Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term used to describe the range of outcomes that result from prenatal exposure to alcohol (ethanol). Behavioral effects may include hyperactivity, attention deficit, impaired sensory processing, and learning and memory problems. People with FASDs may also have difficulties using information flexibly, and this could contribute to deficits in cognition. Such problems are thought to be seated in frontal cortices, including prefrontal cortex, but also require hippocampal input. Devising new strategies for amelioration of these problems has great clinical relevance. Given that deficits in learning and memory have been extensively demonstrated in rodent models of FASD, we examine cognitive flexibility (the ability to “switch mental gears”) in young adults. We propose to continue using our innovative experimental design in which rats exposed to a moderate dose of ethanol prenatally are given choline ± working (short term) memory training during adolescence. The combination of choline + training improves the alcohol-induced deficit in cognitive flexibility but not to the point that performance is equivalent to control animals. In this proposal, we plan to use a mixture of nutrients (that includes choline) that has been shown to provide substrate for dendritic spines in animals and to improve cognitive performance in developing and aging humans. We will assess behavior and brain synaptic protein expression to determine whether our intervention can improve both memory and problem solving and how the effects manifest in the brain in the same animals.

摘要 胎儿酒精谱系障碍（FASD）是一个总括性术语，用于描述胎儿酒精谱系障碍的范围。 产前暴露于酒精（乙醇）的结果。行为影响可能包括 多动症、注意力缺陷、感觉处理受损以及学习和记忆问题。 患有FASD的人也可能难以灵活地使用信息，这可能有助于 认知缺陷。这些问题被认为是位于额叶皮层，包括 前额皮质，但也需要海马输入。制定新的战略， 这些问题具有很大的临床相关性。鉴于学习和记忆的缺陷已经 在FASD的啮齿动物模型中得到广泛证实，我们检查了认知灵活性（ 在年轻的成年人中“转换精神齿轮”）。我们建议继续使用我们的创新 实验设计中，大鼠产前暴露于中等剂量的乙醇， 胆碱±工作（短期）记忆训练在青春期。胆碱和 + 训练可以改善酒精引起的认知灵活性缺陷，但还没有达到这样的程度 性能等同于对照动物。在这个建议中，我们计划使用一种混合营养素 (that包括胆碱），其已被证明为动物中的树突棘提供底物 并改善发育和衰老人类的认知能力。我们将评估行为 和大脑突触蛋白表达来确定我们的干预是否可以改善这两个方面 记忆力和解决问题的能力，以及这些影响如何在同一动物的大脑中表现出来。