Rodent Project

项目四（啮齿动物）将关注于何时以及给予多少铁来预防长期的神经行为

Project IV (rodent) will focus on when and how much iron to give to prevent the long-term neurobehavioral sequelae of early iron deficiency (ID) in experimental rodent models of prenatal or combined pre- and postnatal ID. Long-term effects are consistently observed in human and animal studies of ID in infancy. The proposed project is a logical treatment extension of PPG1 in which we characterized region-specific changes in neural biochemistry, neurotransmitter metabolism, bioenergetics, and behaviors that result from uncompensated ID during gestation and lactation. The proposed project will investigate the optimal timing of dietary iron treatment to reverse or prevent the brain and behavioral effects induced by our model of combined pre- and postnatal ID. The developmental period in question roughly corresponds to the human newborn period and the 1st 6-12 months of postnatal life. An important novel aspect of the experiments will be a further exploration of mechanisms for the persistent effects of early ID. We will determine which developmentally regulated genes/gene products in several brain regions (striatum and hippocampus) are permanently altered in response to early ID. Additionally, we would potentially identify the time(s) at which these expressions become set. There are two Specific Aims. The first is to determine if a dietary iron intervention during early or mid lactation will reliably prevent the long-term brain-behavior effects of early ID. The hypothesis is that different aspects of brain biology and associated behaviors will be sensitive to iron intervention in an age dependent manner. The specific goals are to identify which of the genomic, biochemical, structural and behavioral alterations are resistant to recovery depending on time of iron treatment. The second Specific Aim is to begin to narrow down the dose and time of iron treatment that prevents the long-term neurobehavioral sequelae of early ID without neurotoxicity. We hypothesize that aggressive iron administration following ID in infancy will result in excessive uptake of this potential neurotoxin because of enhanced iron transport processes upregulated by early ID. Aim 2 will identify and compare the brain genomic, biochemical, structural, and behavioral effects of 2 doses of dietary iron from P8 or P15 to P21. The goals of this rodent project are complementary to the other PPG2 projects with respect to the identification of behaviors and neurobiology that can be restored to normal levels with early dietary iron intervention. This information will lead the other PPG2 projects by increasing our understanding of the genomic, biochemical, structural and behavioral changes that occur with early ID and iron treatment.