Enhancement of learning and memory by flavonoids

饮食是最重要的生活方式因素之一，饮食对心血管疾病和神经退行性疾病的发病率有很大影响，因此健康的饮食对健康老龄化至关重要。在过去的几年里，某些食品和饮料中的各种生物活性成分，特别是一类被称为类黄酮的化合物，引起了人们的兴趣。最近的饮食干预研究，特别是那些使用葡萄酒、茶、可可或蓝莓的研究，已经开始证明对血管功能和精神表现的有益影响。虽然这些食品和饮料在化学成分、营养含量和每份卡路里上有很大的不同，但它们有一个共同点，即它们是花青素和黄烷醇这两类黄酮类化合物的主要饮食来源。在人类和动物模型中使用富含这些类黄酮的食物或提取物进行的膳食补充研究表明，它们具有增强记忆和学习的能力。据认为，它们可能通过1)保护脆弱的脑细胞，2)增强现有的脑细胞功能，3)刺激脑细胞再生，或4)触发新脑细胞和/或新血管的生长来达到这一目的。在我们实验室进行的现有人类和动物工作的基础上，这项多学科研究旨在确定特定的黄酮类化合物如何通过关注它们刺激新神经元和血管生长的潜力以及决定这些变化的分子事件来增强记忆和学习。这项研究还将利用行为和最先进的大脑成像(FMRI)技术，提供关于富含黄酮类食物的能力的关键信息，以改善人类老年人的记忆和学习。这一建议的结果对于开发饮食中类黄酮成分的潜在有益健康影响，特别是在对抗与正常和异常衰老有关的人类学习和记忆下降方面具有潜在的有益健康影响。如果我们能够确定哪些类黄酮是最有益的，以及它们在大脑中的作用方式和位置，这将有助于我们制定未来的策略，以最大限度地利用我们食物中的这些膳食制剂，例如，通过开发含有高水平特定类黄酮的植物或新型功能食品。此外，将改进关于食品消费的具体饮食建议，以及防止以假定的保护作用为基础不分青红皂白地销售食品补充剂的准则。该提案将扩大对饮食在防止人脑老化和增强一系列认知能力(例如空间记忆、长期记忆)方面所起作用的理解。这项研究还将为解决认知下降问题的新的和有希望的预防性治疗提供背景。因此，这项研究的结果对老龄化人口具有重要意义，因为人们非常希望增加健康老龄化。此外，生活质量方面的潜在好处与整个人口有关，医疗保健费用的潜在节省也是如此。

Representing one of the most important lifestyle factors, diet can strongly influence the incidence of cardiovascular disease and neurodegenerative diseases and thus a healthy diet is crucial for healthy ageing. Various bioactive constituents of certain foods and beverages, in particular a class of compounds called flavonoids, have generated interest over the last few years. Recent dietary intervention studies, in particular those using wine, tea, cocoa or blueberries, have begun to demonstrate beneficial effects on the function of blood vessels and on mental performance. While such foods and beverages differ greatly in chemical composition, nutrient content and calories per serving, they have in common that they are amongst the major dietary sources of two groups of flavonoids known as anthocyanins and flavanols. Dietary supplementation studies in humans and animal models using foods or extracts rich in these flavonoids have indicated that they possess an ability to enhance memory and learning. It is thought that they may do this by 1) protecting vulnerable brain cells, 2) enhancing existing brain cell function, 3) stimulating brain cell regeneration, or 4) triggering the growth of new brain cells and/or new blood vessels. Building on existing human and animal work conducted in our laboratory, this multidisciplinary study is designed to determine how specific flavonoids may enhance memory and learning by focussing on their potential to stimulate the growth of new neurons and blood vessels, and the molecular events which determine these changes. The study will also provide crucial information on the ability of flavonoid-rich foods to produce improvements in memory and learning in human older adults using both behavioural and state-of-the-art, brain imaging (fMRI) techniques. The outcomes of this proposal have implications for exploiting the potential beneficial health effects of flavonoid components of the diet, particularly with relation to counteracting the decline in human learning and memory which is associated with normal and abnormal ageing. If we are able to determine which flavonoids are the most beneficial, and how and where they work in the brain, this will help us develop future strategies to maximise these dietary agents in our foods, for example, by developing plants or novel functional food products with high levels of specific flavonoids. In addition, specific dietary advice on food consumption will be improved, as will guidelines to prevent the indiscriminate marketing of food supplements on the basis of putative protective effects. The proposal will broaden understanding of the role that diet plays in the prevention of human brain ageing and the enhancement of a range of cognitive abilities (e.g., spatial memory, long-term memory). The study will also provide the background for new and promising preventive treatments for tackling cognitive decline. The results of this study therefore have important implications for an ageing population where an increase in healthy ageing is greatly desired. Moreover, the potential benefits in terms of quality of life are relevant to the population as a whole, as are the potential savings in health care costs.