Brain and Behavior in Early Iron Deficiency

描述（由申请人提供）：本计划-项目拨款（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，并确定干预措施，以纠正或预防短期和长期的不良影响。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，至少同样多的婴儿患有缺铁性贫血。缺铁对各地贫困和/或少数民族母亲和婴儿的影响尤为严重。然而，关于早期缺铁对大脑和行为的影响的研究仍然相对较少。在未来5年，PPG将重点关注：1)缺铁与大脑发育不同阶段的关系；2)干预措施的时机，以改善短期影响并防止对大脑和行为的长期后果；3)对短期和长期影响及其过程的深入研究。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）支持。主要临床和基础科学研究人员之间的跨学科合作将组成项目和核心项目在概念和方法上紧密联系在一起，旨在使每个项目都具有特殊但互补的作用。项目一（人类婴儿）将全面研究人类婴儿出生前后缺铁对大脑和行为的影响以及铁治疗的时机。项目二（戴维斯猴）将继续研究其新发现，即产前缺铁会导致抑制力和冲动性降低的行为特征，尽管有铁补充。项目III（麦迪逊猴子）将关注青春期母亲的婴儿的ID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（发育中的啮齿动物）侧重于不同时期铁治疗在大脑发育中的有效性，以及环境干预在挽救早期ID成年动物的基因组、生化、结构和行为表型方面的潜在益处。所有项目紧密结合，评估神经和行为的发展。单独来说，每个项目都代表着对早期缺铁研究的重大飞跃。总的来说，该项目将在理解、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失调。

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.