HDHL EpiBrain: Epigenetic effects of B-vitamins on brain health throughout life

HDHL EpiBrain：B 族维生素对一生中大脑健康的表观遗传影响

• 批准号: BB/S020330/1
• 负责人: Helene McNulty
• 金额: $ 34.01万
• 依托单位: University of Ulster
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FS020330%2F1
• 关键词: HDHL; EpiBrain; Epigenetic; effects; vitamins

What's already known in this research area: Folic acid and closely related vitamins (vitamin B12, vitamins B6 and riboflavin) are critical for brain health throughout life. Low intakes of these nutrients may impact adversely on brain development in early life and brain function in later life. In early life, folic acid supplements are recommended for women who are trying to become pregnant and during the first 12 weeks of pregnancy in order to reduce the risk of neural tube defects (NTDs) including spina bifida. Apart from preventing NTDs, however, folic acid intake of mums during pregnancy appears to be associated with better cognitive performance in the child, but this aspect is still under investigation by scientists worldwide. The link between nutritional factors such as folic acid in mums during pregnancy and brain health in the child may be explained by 'Epigenetics'. This is the study of processes (such as DNA methylation) that alter our genes by switching them on and off, and we now know that diet can have a major influence on these genetic processes. These changes to our genes happen throughout the lifecycle, from the time of conception, through pregnancy, childhood, middle age and old age. What EpiBrain will address: In order to support health improvement strategies, both for mothers during pregnancy and their babies on one hand, and for adults as they age on the other, we need a better understanding of how folic acid and related B vitamins influence specific genes related to brain development in the child and cognitive function in older adults. This is the overall purpose of the EpiBrain project. How this will be achieved: The EpiBrain project will bring together research teams from the UK Canada and Spain who have strong expertise in nutrition and epigenetics and a track record of working successfully together. Our work will use 'epigenome-wide association studies' or EWAS, an approach that involves rapidly scanning complete sets of DNA to find epigenetic marks linked with health. This approach is necessary to more fully explore the biological basis explaining the impacts of maternal folic acid supplementation in pregnancy on brain development in the child, and interventions with B vitamins to improve cognitive function in later life. We will conduct new epigenetics analysis on stored samples from studies previously conducted by our research teams in pregnancy and older age. Dietary, nutritional and epigenetic data will be linked with cognitive function measurements in children and older adults. Brain function assessment will also include neuroimaging data using state-of-art magnetoencephalography (MEG) conducted in early and late life on our study participants, providing a direct measure of brain activity. Why the results of the EpiBrain project are important: The EpiBrain project will lead to improved understanding of the role of folic acid and other B vitamins, their epigenetic effects and brain function in childhood and older age, with expected results anticipated to provide scientific substantiation to support nutritional strategies for sustaining better brain health through the lifespan. This project is very timely because of potential imminent changes in fortification and supplementation policies. The implementation of mandatory food fortification for NTD prevention is currently being debated at national levels in the UK and Ireland, while the team in Canada is working on challenges and solutions for the generating guidelines in relation to the amount of folic acid to incorporate into folic acid supplements for pregnant women. The EpiBrain project provides a unique opportunity for a truly transnational collaboration to study the potential effects of folic acid (that may be mediated by Epigenetics) on brain health throughout the lifecycle.

在这个研究领域已经知道：叶酸和密切相关的维生素（维生素B12，维生素B6和核黄素）对整个生命的大脑健康至关重要。这些营养素的低摄入量可能会对生命早期的大脑发育和晚年的大脑功能产生不利影响。在生命的早期，叶酸补充剂被推荐给试图怀孕的女性和怀孕的前12周，以降低神经管缺陷（NTD）的风险，包括脊柱裂。然而，除了预防NTD外，母亲在怀孕期间摄入叶酸似乎与儿童更好的认知能力有关，但这方面仍在由世界各地的科学家进行调查。怀孕期间母亲的叶酸等营养因素与儿童的大脑健康之间的联系可以用“表观遗传学”来解释。这是对通过打开和关闭基因来改变我们基因的过程（如DNA甲基化）的研究，我们现在知道饮食可以对这些遗传过程产生重大影响。我们基因的这些变化发生在整个生命周期中，从受孕到怀孕、童年、中年和老年。Epibrain将解决的问题：为了支持改善健康的战略，无论是在怀孕期间的母亲和他们的婴儿一方面，并为成年人，因为他们的年龄，另一方面，我们需要更好地了解叶酸和相关的B族维生素如何影响特定的基因有关的大脑发育的儿童和老年人的认知功能。这是EpiBrain项目的总体目标。如何实现这一目标：EpiBrain项目将汇集来自英国、加拿大和西班牙的研究团队，他们在营养和表观遗传学方面具有很强的专业知识，并有成功合作的记录。我们的工作将使用“表观基因组关联研究”或EWAS，这种方法涉及快速扫描完整的DNA集，以找到与健康相关的表观遗传标记。这种方法是必要的，以更充分地探索生物学基础，解释母亲在怀孕期间补充叶酸对儿童大脑发育的影响，以及用B族维生素干预以改善晚年的认知功能。我们将对我们的研究团队先前在怀孕和老年期间进行的研究中储存的样本进行新的表观遗传学分析。饮食、营养和表观遗传数据将与儿童和老年人的认知功能测量相关联。脑功能评估还将包括使用最先进的脑磁图（MEG）在我们的研究参与者的早期和晚期进行的神经成像数据，提供大脑活动的直接测量。为什么EpiBrain项目的结果是重要的：EpiBrain项目将导致更好地了解叶酸和其他B族维生素的作用，其表观遗传效应和儿童和老年人的大脑功能，预期结果预计将提供科学依据，以支持营养策略，在整个生命周期中维持更好的大脑健康。该项目非常及时，因为强化和补充政策可能即将发生变化。目前，英国和爱尔兰正在国家一级讨论为预防NTD实施强制性食品强化，而加拿大的团队正在研究制定孕妇叶酸补充剂中叶酸含量指南的挑战和解决方案。EpiBrain项目为真正的跨国合作提供了一个独特的机会，以研究叶酸（可能由表观遗传学介导）对整个生命周期大脑健康的潜在影响。

项目成果

Effect of folic acid supplementation during pregnancy on brain health of the child at 11 years: the FASSTT Offspring trial

怀孕期间补充叶酸对 11 岁儿童大脑健康的影响：FASSTT Offspring 试验

• DOI: 10.1017/s0029665120004553
• 发表时间: 2020
• 期刊: Proceedings of the Nutrition Society
• 影响因子: 7
• 作者: Caffrey A

Additional file 1 of Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial

妊娠中期和晚期母亲补充叶酸对儿童神经认知发育的影响的附加文件 1：随机对照试验的 11 年随访

• DOI: 10.6084/m9.figshare.14190194
• 发表时间: 2021
• 作者: Caffrey A

Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial.

• DOI: 10.1186/s12916-021-01914-9
• 发表时间: 2021-03-10
• 期刊: BMC medicine
• 影响因子: 9.3
• 作者: Caffrey A;McNulty H;Rollins M;Prasad G;Gaur P;Talcott JB;Witton C;Cassidy T;Marshall B;Dornan J;Moore AJ;Ward M;Strain JJ;Molloy AM;McLaughlin M;Lees-Murdock DJ;Walsh CP;Pentieva K
• 通讯作者: Pentieva K