Newborn Iron Deficiency

描述（由申请人提供）：缺铁仍然是世界上儿童最重要的营养缺乏症之一。虽然有40多项研究描述了出生后获得性膳食缺铁对神经发育的影响，但对胎儿和新生儿脑缺铁的直接和长期后遗症的关注较少。胎儿/新生儿缺铁发生在三种临床条件下：严重的母体缺铁，宫内发育迟缓（IUGR）和妊娠合并糖尿病。在发展中国家，前者使30 - 50%的怀孕复杂化。后两种原因导致美国每年有22.5万名新生儿缺铁。铁缺乏至少影响早期脑发育的三个主要方面：能量代谢、单胺神经递质稳态和髓鞘形成。我们的实验室专注于前者，因为它与发育中的海马体有关;海马体是促进外显记忆的主要神经回路。影响早期海马发育的营养损伤（例如缺铁）可能会损害记忆功能。我们的长期目标是了解胎儿晚期和产后早期铁缺乏改变海马的生物化学、结构、细胞信号传导和电输出的机制，以及这反过来如何改变基于海马的记忆行为。我们的具体目标是证明胎儿/新生儿铁缺乏1）引起糖尿病母亲的人类婴儿在出生时和铁补充后6、12、18和24个月的识别记忆异常，如事件相关电位和行为任务所记录的;和2）改变海马生物化学，减少树突分支、神经元细胞信号传导激酶浓度和长时程增强，并在缺铁和铁补充后损害大鼠脑内依赖的微量条件反射。为了了解铁对海马的具体影响，我们将开始确定潜在的转录和转录后机制，铁调节特定目标2中确定的关键海马结构和功能蛋白。

DESCRIPTION (provided by applicant): Iron deficiency remains one of the foremost nutrient deficiencies in children in the world. Whereas over 40 studies have described the effects of postnatally acquired dietary iron deficiency on neurodevelopment, less attention has been paid to the immediate and long-term sequelae of fetal and neonatal brain iron deficiency. Fetal/neonatal iron deficiency occurs in three clinical conditions; severe maternal iron deficiency, intrauterine growth retardation (IUGR) and pregnancies complicated by diabetes mellitus. The former complicates 30-50% of pregnancies in the developing world. The latter two account for iron deficiency in 225,000 newborn infants per year in the US. Iron deficiency affects at least three major aspects of early brain development: energy metabolism, monoamine neurotransmitter homeostasis, and myelination. Our laboratory has focused on the former as it relates to the developing hippocampus; the major neural circuit that subserves explicit memory. Nutritional insults (e.g. iron deficiency) that affect early hippocampal development are likely to impair memory function. Our long term objectives are to understand the mechanisms by which late fetal and early postnatal iron deficiency alter the biochemistry, structure, cell signaling, and electrical output of the hippocampus and how this in turn alters hippocampally based memory behavior. Our specific aims are to demonstrate that fetal/neonatal iron deficiency 1) causes abnormalities in recognition memory in human infants of diabetic mothers at birth and following iron repletion at 6, 12, 18 and 24 months as documented by event related potentials and behavioral tasks; and 2) alters hippocampal biochemistry, decreases dendritic arborization, neuronal cell-signaling kinase concentrations and long-term potentiation, and impairs hippocampally dependent trace conditioning in the rat while iron deficient and following iron repletion. In order to understand the specific effect of iron on the hippocampus, we will begin to identify potential transcriptional and post-transcriptional mechanisms by which iron regulates key hippocampal structural and functional proteins identified in specific aim 2.