Nutrient combination to mitigate Fetal Alcohol Spectrum Disorder

摘要 胎儿酒精谱系障碍(FASD)是一个总括术语，用来描述 胎儿期接触酒精(酒精)造成的后果。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的人也可能在灵活使用信息方面存在困难，这可能有助于 与认知缺陷有关。这类问题被认为存在于额叶皮质，包括 前额叶皮质，但也需要海马区的输入。制定新的战略来改善 这些问题具有很大的临床意义。考虑到学习和记忆方面的缺陷 在FASD的啮齿动物模型中，我们广泛展示了认知灵活性(能力 以“改变精神状态”)。我们建议继续使用我们的创新产品 实验设计给出了产前暴露于中等剂量乙醇的大鼠 胆碱±工作(短期)记忆训练在青春期。胆碱的联合作用 +训练改善了酒精引起的认知灵活性缺陷，但没有达到 表演相当于控制动物。在这项提案中，我们计划使用一种营养素的混合物 (包括胆碱)已被证明为动物树突棘的底物 并改善发育和老龄化人类的认知能力。我们将对行为进行评估 和脑突触蛋白的表达来确定我们的干预是否可以改善两者 记忆和解决问题，以及这些影响如何在相同动物的大脑中表现出来。

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.