Rodent Project

项目四(啮齿动物)将专注于何时以及摄入多少铁来预防长期的神经行为 孕前和孕期联合用药对实验性缺铁(ID)鼠的后遗症 在人类和动物对婴儿期ID的研究中，持续观察到出生后ID的长期影响。这个 建议的项目是PPG1的合乎逻辑的处理扩展，其中我们描述了特定地区的变化 在神经生物化学、神经递质代谢、生物能量学和由 妊娠期和哺乳期无偿缺乏症。拟议的项目将调查以下最佳时机 膳食铁治疗逆转或预防由我们的模型引起的大脑和行为影响 出生前和出生后的ID。所述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是 将进一步探索早期ID持续影响的机制。我们将确定 几个大脑区域(纹状体和海马体)的发育调节基因/基因产物是 永久改变，以响应早期ID。此外，我们可能会确定时间(S) 这些表情就成了定式。 有两个具体目标。第一个是确定是否在早期或中期进行膳食铁干预 哺乳可以可靠地防止早期失调症对大脑行为的长期影响。 在年龄依赖的情况下，大脑生物学和相关行为的某些方面将对铁干预敏感 举止。具体目标是确定基因组、生化、结构和行为中的哪一种 根据铁治疗的时间不同，改变是不能恢复的。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，在婴儿时期服用攻击性铁剂后， 导致过量摄取这种潜在的神经毒素，因为铁的运输过程增强 由早期ID上调。AIM 2将识别和比较大脑基因组、生化、结构和 从P8或P15到P21两种剂量的膳食铁对行为的影响。 这一啮齿动物项目的目标与其他PPG2项目在以下方面是互补的 早期膳食铁可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PPG2项目的了解来引导其他PPG2项目 基因组、生化、结构和行为的改变在早期缺铁和铁治疗中发生。

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.