Brain and Behavior in Early Iron Deficiency

这项计划-项目补助金（PPG）的总体目的是了解缺铁如何改变大脑 和早期发展中的行为，并确定在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%的妇女在怀孕期间贫血，其中约一半是由于铁 缺陷在发展中国家，46-66%的4岁以下儿童贫血，其中一半归因于 铁缺乏症和铁缺乏症对贫穷和/或少数民族母亲和婴儿的影响不成比例 到处然而，关于早期糖尿病对大脑和行为的影响， 缺铁在接下来的5年里，PPG将重点关注1）与不同的铁缺乏症相关的时间 脑发育的阶段，2）铁补充的时机，以改善短期影响，并防止长期 对大脑和行为的影响，以及3）对短期和长期影响的深入研究， 过程来解释它们。PPG涉及4个项目（1个人类婴儿，2个猴，1个啮齿动物），由 3个核心（行政、分析和统计）。 领先的临床和基础科学研究人员之间的合作，在概念上紧密相连， 从方法上讲，每一个都有一个特殊但互补的作用。项目I（人类婴儿）将 是一个系统的调查大脑和行为的影响，产前v.产后v.结合产前和 人类婴儿出生后缺铁和铁治疗的时机。项目II（戴维斯猴）将使用 一个实验模型，以追求其新颖的发现，产前缺铁产生的行为概况 抑制力降低冲动性增加尽管铁元素充足项目III（麦迪逊猴）将 评估出生前和出生后铁缺乏对婴儿大脑行为的影响 母亲-与弱势群体直接相关的自然主义模式（发展中国家， 青少年母亲）。项目四（啮齿动物的开发）将侧重于铁治疗在不同环境下的有效性。 在防止基因组，生物化学，结构和行为改变， 成年它还将考虑在早期铁摄入过多后， 缺陷通过紧密结合，所有项目都评估神经和行为发育。均使用 评估大脑的创新方法（例如，项目I中的电生理学，药物激发的PET， 项目II中的脑组织，项目III中的区域基因组学）。每个项目，每个项目 这是对早期缺铁研究的重大突破。总体而言，该计划 将为理解、治疗和预防铁对大脑和行为的影响做出重大贡献。 缺乏症，世界上最常见的单一营养素紊乱。

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.