Iron deprivation will be studied in rhesus monkeys as a model for the public health problem of developmental iron deficiency anemia (IDA) and infant cognitive disorders. At present it is not known whether IDA as recognized in human infants can be reproduced by dietary iron deprivation in a suitable animal model. Iron deficiency will be induced during two different developmental periods, the period of peak brain growth and the period of peak myelination, by using iron deficient diet and infant formula. These two iron deprived groups will be compared to controls fed an adequate iron diet (n=16/group). Intensive infant evaluations (birth to 10 months of age) will focus on tests that reflect three possible substrates on iron infant evaluations (birth to 10 months of age) will focus on tests that reflect three possible substrates of iron deficiency-induced brain dysfunction, delayed myelination, altered hippocampal function, and changes in responsiveness of brain dopamine systems. Specific assessments include: for myelination, auditory brainstem response, fine motor development, acuity, and MRI scan with white matter quantification; for hippocampal function, spatial maze performance; for dopamine, salivary prolactin, eyeblink, eyeblink rate, response of schedule-controlled behavior to dopamine agonists and antagonists. Other measures are taken to provide context for these assessment, such as weight gain, food intake, somatic and gross motor development, neonatal neurobehavioral status, plasma essential trace elements, and daily health records. The impact of iron deprivation on the hematological system will be determined through measures in pregnant monkey dams, fetuses and infants. Through coordination with other program project grants, we hope to provide information on the biological basis of cognitive dysfunction seen in infants with iron deficiency anemia.
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