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.
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