Rodent Project

项目IV（啮齿类动物）将重点关注何时以及给予多少铁，以防止长期的神经行为 在产前或产前和产前联合的实验啮齿动物模型中早期铁缺乏（ID）的后遗症 在婴儿期ID的人类和动物研究中始终观察到长期影响。的 拟议的项目是PPG 1的合理治疗扩展，其中我们描述了区域特异性变化 在神经生物化学，神经递质代谢，生物能量学，以及由 在妊娠期和哺乳期的无补偿ID。拟议的项目将研究 饮食铁治疗，以扭转或防止我们的模型诱导的大脑和行为的影响， 结合产前和产后ID。所讨论的发育期大致对应于人类 新生儿期和出生后6-12个月。实验的一个重要的新方面将 进一步探索早期ID持续影响的机制。我们将确定 发育调控基因/基因产物在几个脑区（纹状体和海马）， 永久性改变，以响应早期ID。此外，我们可能会确定的时间（S）， 这些表达变得固定。 有两个具体目标。第一个是确定饮食铁干预是否在早期或中期 哺乳将可靠地防止早期ID的长期脑行为影响。 脑生物学和相关行为的方面将对年龄依赖的铁干预敏感。 方式具体目标是确定哪些基因组，生化，结构和行为 根据铁处理的时间，改变抵抗恢复。第二个具体目标是开始 缩小铁治疗的剂量和时间，以防止长期的神经行为后遗症， 早期ID无神经毒性。我们假设婴儿期ID后积极的铁管理将 由于增强的铁转运过程， Aim 2将识别和比较大脑基因组，生物化学，结构， 从P8或P15到P21的2个剂量的膳食铁的行为效应。 本啮齿类动物项目的目标是对PPG 2其他项目的补充， 早期饮食铁可以恢复到正常水平的行为和神经生物学鉴定 干预这些信息将通过增加我们对PPG 2项目的理解， 基因组、生物化学、结构和行为的变化与早期ID和铁治疗有关。

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.