IN VIVO EFFECT OF CHRONIC HYPOXIA ON THE NEUROCHEMICAL PROFILE OF THE DEVELOPIN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 存在妊娠获得性围产期铁缺乏风险的人类婴儿的认知缺陷表明，发育中的海马体参与其中。为了解围产期缺铁大鼠海马区损伤的合理生物学解释，应用核磁共振氢谱对缺铁大鼠海马区16种代谢物的神经化学分布进行了纵向研究。18只缺铁大鼠和16只缺铁大鼠在出生后7天、PD10、PD14、PD21和PD28以11-24微L体积的海马区代谢物定量。围产期缺铁是通过在妊娠d3至d7期间给妊娠母鼠喂食缺铁饮食而引起的。缺铁组大鼠脑组织铁浓度在第7天和第28天分别降低60%和19%(P均0.001)。在两组患者中，16种代谢物中有12种的浓度在PD7和PD28之间随时间变化(P均为0.001)。与缺铁组相比，缺铁组的磷酸肌酸、谷氨酸、N-乙酰天冬氨酸、天冬氨酸、γ-氨基丁酸、磷酸乙醇胺和牛磺酸浓度及磷酸肌酸/肌酸比值均升高(P0.02)。这些神经化学变化表明，围产期缺铁在静息能量状态、神经传递和髓鞘形成方面存在持续变化。发育中的海马体的神经化学特征的改变可能是围产期缺铁婴儿的一些认知缺陷的基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cognitive deficits in human infants at risk for gestationally acquired perinatal iron deficiency suggest involvement of the developing hippocampus. To understand the plausible biological explanations for hippocampal injury in perinatal iron deficiency, a neurochemical profile of 16 metabolites in the iron-deficient rat hippocampus was evaluated longitudinally by 1H NMR spectroscopy at 9.4 T. Metabolites were quantified from an 11-24 microL volume centered in the hippocampus in 18 iron-deficient and 16 iron-sufficient rats on postnatal day (PD) 7, PD10, PD14, PD21 and PD28. Perinatal iron deficiency was induced by feeding the pregnant dam an iron-deficient diet from gestational d 3 to PD7. The brain iron concentration of the iron-deficient group was 60% lower on PD7 and 19% lower on PD28 (P 0.001 each). The concentration of 12 of the 16 measured metabolites changed over time between PD7 and PD28 in both groups (P 0.001 each). Compared with the iron-sufficient group, phosphocreatine, glutamate, N-acetylaspartate, aspartate, gamma-aminobutyric acid, phosphorylethanolamine and taurine concentrations, and the phosphocreatine/creatine ratio were elevated in the iron-deficient group (P 0.02 each). These neurochemical alterations suggest persistent changes in resting energy status, neurotransmission and myelination in perinatal iron deficiency. An altered neurochemical profile of the developing hippocampus may underlie some of the cognitive deficits observed in human infants with perinatal iron deficiency.