Project Title: Brain Development and Iron Deficiency (Project 3 of Brain and Behavior in Early Iron Deficiency) Principal Investigator: Christopher Coe, PhD The 5-year Program-Project grant addresses unresolved questions about the developmental effects of iron deficiency of brain and behavior in infancy. Driven by new pediatric concerns, and the widespread prevalence of anemia worldwide, the program targets CNS processes of myelination, neurotransmission, neuronal metabolism, particular brain regions (hippocampus and basal ganglia, especially striatum) and associated behaviors. The program considers the effects of the timing of iron deficiency, both fetal and postnatal, and its treatment. The component projects, with inter-disciplinary collaboration among leading clinical and basic science researchers, are tightly linked conceptually and methodologically, and designed so that each project has a special but complementary role. Project I (human infant) emphasizes promising new noninvasive ways to assess CNS functions in babies. Project II (monkey infant-Davis) and Project III (monkey infant-Madison) use hematological and behavioral measures that complement Project I, and compare a prenatal vs. postnatal induction of anemia in two different primate models. Project II involves diet-induced discrete time periods of iron deficiency in the nursing infant, whereas Project III involves a low placental transmission of iron stores to the fetus, and infant growth induced iron needs that will exceed dietary intake.  The timing and conditions of iron deficiency and its treatment are thus systematically varied in the two models. Cerebrospinal fluid analyses, drug challenge studies, electrophysiology, and neuroimaging are utilized to assess brain development. Project IV (rodent) investigates comparable developmental periods and behavioral functions, and includes tissue and imaging analyses to clarify underlying mechanisms. Individually, each project represents a substantial leap beyond any previous research on early iron deficiency. Collectively, the program is making a major contribution to understanding developmental consequences of iron deficiency, the world's most common single nutrient disorder.

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