Dietary supplementation in animal models of neurodevelopmental disorders

与胎儿酒精综合症(FAS)和注意力缺陷多动障碍(ADHD)相关的行为问题包括学习和记忆方面的困难。我们使用动物模型来理解这些疾病背后的生物学机制，研究特定的膳食补充剂是否被证明是有效的预防和/或康复干预。我们已经证明，如果幼年大鼠在大脑发育最快的时期暴露于酒精中，它们将出现短期记忆障碍，这与海马体基因表达的变化有关，海马体是大脑中与记忆存储相关的区域。幼年大鼠饮食中胆碱含量的增加已被证明会导致记忆增强和海马体中生长因子的增加。因此，我们建议研究这种饮食治疗是否会对酒精暴露的大鼠的记忆过程产生有益的影响。为此，我们将给幼鼠喂食等量的酒精，相当于重度“酗酒”孕妇的饮酒量，同时补充她们的饮食中的胆碱。我们预计，这些大鼠在水迷宫中对隐藏逃生平台的位置将表现出比服用乙醇而不是胆碱的大鼠更好的短期记忆；我们还预计饮食治疗将逆转它们大脑中看到的变化。我们还在完成一系列关于自发性高血压大鼠(SHR，ADHD的公认动物模型)学习和记忆的研究。我们的初步发现表明，与正常大鼠相比，自发性高血压大鼠在学习任务中犯下更多错误，不是因为它们无法记忆，而是因为它们无法抑制错误的反应。这些老鼠还表现出大脑脂肪酸组成的异常，这可能反过来通过影响特定的化学信使而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)，看看我们是否可以改善它们的行为能力。这些研究的发现可能会对他们所模拟的人类状况产生有益的影响。

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.