Brain and Behavior in Early Iron Deficiency

该项目资助（PPG）的总体目的是了解缺铁如何改变早期发育中的大脑和行为，并确定短期和长期纠正或预防不良影响的干预措施。全世界超过50%的妇女在怀孕期间贫血，主要是由于缺铁; 20-25%的婴儿患有缺铁性贫血，至少有同样多的婴儿患有缺铁性贫血而没有贫血。缺铁对世界各地的贫穷和/或少数民族母亲和婴儿的影响不成比例。然而，关于早期缺铁对大脑和行为影响的研究仍然相对较少。在接下来的5年里，PPG将重点关注1）与大脑发育不同阶段相关的铁缺乏的时间，2）改善短期影响并防止对大脑和行为的长期影响的干预措施的时间，以及3）对短期和长期影响的深入研究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（管理，分析和统计）支持。组成项目和核心，与领先的临床和基础科学研究人员的跨学科合作，在概念和方法上紧密联系，设计，使每个都有一个特殊的，但互补的作用。项目I（人类婴儿）将全面调查人类婴儿出生前和出生后缺铁对大脑和行为的影响以及铁治疗的时机。项目II（戴维斯猴）将继续其新的发现，产前缺铁产生了减少抑制和冲动的行为概况，尽管铁补充。项目III（麦迪逊猴）将重点关注青春期母亲的婴儿ID的后果，确定经验丰富的母亲的缓冲作用，并考虑铁治疗的有效性取决于时间和孕前铁状态。项目IV（开发啮齿动物）的重点是铁治疗在大脑发育的不同时间的有效性和环境干预在挽救早期ID成年动物的基因组，生物化学，结构和行为表型的潜在好处。单独来看，每个项目都代表了早期缺铁研究的重大飞跃。总的来说，该计划将在理解，治疗和预防缺铁对大脑和行为的影响方面做出重大贡献，缺铁是世界上最常见的单一营养素紊乱。

DESCRIPTION (provided by applicant): 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 short and long-term. Over 50% of women worldwide are anemic during pregnancy, largely due to iron deficiency; 20-25% of the infants have iron-deficiency anemia and at least as many have iron deficiency without anemia. Iron deficiency disproportionately affects poor and/or minority mothers and infants everywhere. Yet there is still relatively little research on 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 interventions to ameliorate short-term effects and prevent long-term 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 comprehensive investigation of brain and behavior effects of pre v. postnatal iron deficiency in human infants and the timing of iron treatment. Project II (Davis monkey) will pursue its novel finding that prenatal iron deprivation produced a behavioral profile of reduced inhibition and impulsivity, despite iron repletion. Project III (Madison monkey) will focus on consequences of ID in infants of adolescent mothers, identify buffering effects of experienced mothering, and consider effectiveness of iron therapy depending on timing and preconception iron status. Project IV (developing rodent) focuses on the effectiveness of iron therapy at different times in brain development and potential benefits of environmental intervention in rescuing the genomic, biochemical, structural, and behavioral phenotypes in adult animals with early ID. With close integration, all projects assess neural and behavioral development. Individually, each project represents a substantial leap beyond previous research on early iron deficiency. Collectively, the program will make a major contribution in understanding, treating, and preventing brain and behavior effects of iron deficiency, the world's most common single nutrient disorder.