Brain and Behavior in Early Iron Deficiency

这项计划项目拨款(PPG)的总体目的是了解缺铁如何改变大脑。 和早期发育中的行为，并确定在短期和短期内纠正或预防不良影响的干预措施 长期的。全世界高达75%的女性在怀孕期间患有贫血，其中约一半是由于铁引起的 缺乏症。在发展中国家，46%-66%的4岁以下儿童患有贫血，其中一半又被归因于 缺铁和缺铁对贫穷和/或少数族裔母亲和婴儿的影响不成比例 到处都是。然而，关于早期睡眠对大脑和行为的影响，仍有一些重要的问题没有得到解答 缺铁。在接下来的5年里，PPG将专注于1)与不同疾病相关的铁缺乏的时间 大脑发育阶段，2)适时补充铁以改善短期效果并防止长期影响 对大脑和行为的影响，以及3)深入研究短期和长期影响以及 解释它们的过程。PPG涉及4个项目(1个人类婴儿、2个猴子、1个啮齿动物)，由 3个核心(行政、分析和统计)。组成项目和核心，具有跨学科 领先的临床和基础科学研究人员之间的合作，在概念上紧密联系在一起， 在方法论上，设计得使每个人都有特殊但互补的作用。项目I(人类婴儿)将 产前与产后相结合对脑部及行为影响的系统研究 人类婴儿出生后铁缺乏和铁治疗的时机。项目二(戴维斯猴子)将使用 一种实验模型，以追求其新发现，产前缺铁会产生行为特征 减少抑制力和增加冲动，尽管铁的补充。项目III(麦迪逊猴子)将 评估婴幼儿出生前后联合缺铁对脑行为的影响 母亲--与弱势人群直接相关的自然主义模式(发展中国家， 青春期母亲)。项目四(发展中的啮齿动物)将侧重于铁疗法在不同地区的有效性 大脑发育在防止基因组、生化、结构和行为改变方面的时间 成人期。它还将考虑在早期铁之后摄入过多铁可能造成的神经毒性 缺乏症。通过紧密集成，所有项目都可以评估神经和行为发育。各自使用 评估大脑的创新方法(例如，项目I中的电生理学、药物挑战中的PET 项目II、项目III中的脑组织和项目IV中的区域基因组学)。单独地，每个项目 这比之前关于早期缺铁的研究有了很大的飞跃。总体而言，该计划 将对了解、治疗和预防铁对大脑和行为的影响做出重大贡献 缺乏症是世界上最常见的单纯性营养障碍。

The overall purposes of this program-project grant (PPG) are to understand how iron deficiency alters brain and behavior in early development and identify interventions that will correct or prevent ill effects in the shortand long-term. Up to 75% of women worldwide are anemic during pregnancy, with about half due to iron deficiency. In developing countries, 46-66% of children < 4 years are anemic, again with half attributed to iron deficiency, and iron deficiency disproportionately affects poor and/or minority mothers and infants everywhere. Yet there are still important unanswered questions about the brain and behavior effects of early iron deficiency. In the next 5 years, the PPG will focus on 1) timing of iron deficiency in relation to different stages of brain development, 2) timing of iron repletion to ameliorate short-term effects and prevent longterm consequences for brain and behavior, and 3) in-depth study of short- and long-term effects and the processes that account for them. PPG involves 4 projects (1 human infant, 2 monkey, 1 rodent) supported by 3 cores (administrative, analytical, and statistical).The component projects and cores, with interdisciplinary collaboration among leading clinical and basic science researchers, are tightly linked conceptually and methodologically, designed so that each has a special but complementary role. Project I (human infant) will be a systematic investigation of brain and behavior effects of pre- v. postnatal v. combined pre- and postnatal iron deficiency in human infants and the timing of iron treatment. Project II (Davis monkey) will use an experimental model to pursue its novel finding that prenatal iron deprivation produced a behavioral profile of reduced inhibition and increased impulsivity, despite iron repletion. Project III (Madison monkey) will assess brain-behavior effects of combined pre- and postnatal iron deficiency in infants born to young mothers - a naturalistic model directly relevant to vulnerable human populations (developing countries, adolescent mothers). Project IV (developing rodent) will focus on the effectiveness of iron therapy at different times in brain development in preventing genomic, biochemical, structural, and behavioral alterations in adulthood. It will also consider the potential for neurotoxicity with too much iron following early iron deficiency. With close integration, all projects assess neural and behavioral development. Each uses innovative approaches to assess the brain (e.g., electrophysiology in Project I, PET with drug challenge in Project II, brain tissue in Project III, and regional genomics in Project IV). Individually, each project represents a substantial leap beyond previous research on early iron deficiency. Collectively, the program will make major contributions to understanding, treating, and preventing brain and behavior effects of iron deficiency, the world's most common single nutrient disorder.