Dietary supplementation in animal models of neurodevelopmental disorders

与胎儿酒精综合症（FAS）和人类注意力缺陷多动障碍（ADHD）相关的行为问题包括学习和记忆困难。我们使用动物模型来了解这些疾病的生物学机制，以确定特定的膳食补充剂是否可以作为预防和/或康复干预措施。我们已经证明，如果幼鼠在大脑发育最快的时期接触乙醇，它们的短期记忆会出现损伤，这与海马体中基因表达的变化有关，海马体是大脑中与记忆储存有关的区域。研究表明，幼鼠饮食中胆碱含量的增加可以增强记忆，并增加海马体中的生长因子。因此，我们建议研究这种饮食治疗是否会对乙醇暴露大鼠的记忆过程产生有益的影响。为此，我们将给幼鼠喂食相当于重度“狂饮”孕妇所消耗的乙醇量，同时在它们的饮食中补充胆碱。我们预计，这些老鼠对水迷宫中隐藏的逃生平台的位置的短期记忆会比喂食乙醇的老鼠更好，但胆碱没有；我们还希望饮食治疗能够逆转他们大脑中的变化。我们也正在完成一系列关于自发性高血压大鼠（SHR，一种公认的多动症动物模型）学习和记忆的研究。我们的初步研究结果表明，与正常的大鼠相比，SHR在学习任务中犯了更多的错误，不是因为它们不能记忆，而是因为它们不能抑制错误的反应。这些老鼠大脑的脂肪酸组成也表现出异常，这可能反过来又通过对特定化学信使的影响与它们的行为问题有关。因此，我们建议在这些大鼠的饮食中补充二十二碳六烯酸（DHA，一种omega-3脂肪酸），看看我们是否能改善它们的行为能力。这些研究的发现可能对它们所模拟的人类状况有有益的启示。

The behavioural problems associated with Fetal Alcohol Syndrome (FAS) and Attention Deficit Hyperactivity disorder (ADHD) in humans include difficulties with learning and memory. We use animal models to understand the biological mechanisms underlying these conditions, addressing whether specific dietary supplements may prove useful as preventive and/or rehabilitative interventions.We have shown that if young rats are exposed to ethanol during the time when their brain is growing most rapidly, they will show impairments in short-term memory that are related to changes in gene-expression in the hippocampus, a brain region associated with memory storage. An increase in the amount of choline in the diet of young rats has been shown to result in memory enhancement and an increase in growth factors in the hippocampus. Thus we propose to examine whether such dietary treatment will have beneficial effects on memory proceses in ethanol-exposed rats. To this end we will feed young rats amounts of ethanol equivalent to those consumed by heavy "binge-drinking" pregnant women and at the same time supplement their diets with choline. We expect that these rats will show better short-term memory for the location of a hidden escape platform in a water-maze than rats fed ethanol, but not choline; we also expect that the dietary treatment will  reverse the changes seen in their brains.We are also in the process of completing a series of studies on learning and memory in spontaneously hypertensive rats (SHR, a recognised animal model of ADHD). Our preliminary findings indicate that, in comparison to normal rats, SHR make more mistakes on learning tasks, not because they are unable to remember, but because they cannot inhibit the wrong response. These rats also show abnormalities in the fatty acid composition of their brain, which may in turn be related to their behavioural problems through effects on specific chemical messengers. Thus we propose to supplement the diet of these rats with docosahexaenoic acid (DHA, an omega-3 fatty acid) to see whether we can improve their behavioural capabilities. The findings from these studies may have useful implications for the human conditions that they model.