Project III (Madison monkey) will assess brain-behavior effects of combined pre- and postnatal iron deficiency (ID) in infants born to young mothers - a naturalistic model directly relevant to vulnerable human populations (e.g., developing countries, adolescent mothers). Infants of young mothers are at higher risk for ID and anemia because of the competition between maternal and fetal needs during pregnancy, which provides an opportunity to assess the effects of ID that begins in the prenatal period and becomes more manifest in postnatal life. The proposed research builds upon previous studies documenting a high occurrence of ID in infant rhesus monkeys, even from multiparous mothers, which was shown to be induced by an inadequate placenta! transfer of maternal iron and the infant's growth demands for iron exceeding dietary intake from breast milk. Three longitudinal studies will be conducted to address the following aims:
Aim 1 will compare behavioral and cognitive development in monkey infants born to young ID or nonanemic control mothers that consumed either a marginal iron or iron-sufficient diet during pregnancy. Behavioral and developmental outcome will be related to neurobiological and hematological measures.
Aim 2 will directly assess immediate and long-term CMS effects of combined pre- and postnatal ID. Brain tissue studies at weaning and the human equivalent of preschool will determine the impact on myelination, dendritic arborization, and neurochemistry, with a focus on the hippocampus and monoamine activity. CSF proteomics will pursue PPG1 findings that ID animals have a distinctive protein profile in the intrathecal compartment. WBC proteomics will parallel human and Davis monkey projects to study iron regulation and the dopaminergic system.
Aim 3 will determine reversibility of effects with iron supplementation starting at mid-lactation (3 months of age, corresponding to around 9 months in the human infant). Each monkey infant will be evaluated with a standardized battery of tests, including measures of attentional processes, emotional reactivity, cognitive performance, social competence in peer relations, and stress vulnerability. Hematological testing will be conducted routinely during pregnancy, and on each infant from birth through the typical return to a normal hematology by one year of age, which corresponds to the preschool age child. Project III complements the other rodent, monkey and human studies in Program Project Grant (PPG2). It will support the 1st tissue studies of the ID primate brain. The project also highlights the concerns about ID in more vulnerable populations and provides an opportunity to evaluate the effects of ID on the development of brain and behavioral processes in a controlled animal model that spans the pre- and postnatal periods.
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