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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 有妊娠获得性围产期铁缺乏风险的人类婴儿的认知缺陷提示发育中的海马参与。为了了解围产期缺铁引起海马损伤的合理生物学解释，在9.4 T下，通过1H NMR光谱纵向评价了缺铁大鼠海马中16种代谢物的神经化学谱。在出生后第7天（PD）、PD 10、PD 14、PD 21和PD 28，对18只缺铁和16只缺铁大鼠海马中11-24微升体积的甲硫氨酸进行定量。围产期铁缺乏症是由喂养孕母铁缺乏的饮食从妊娠d 3至PD 7。缺铁组的脑铁浓度在PD 7时降低60%，在PD 28时降低19%（均P 0.001）。在两组中，PD 7和PD 28之间，16种测定代谢物中有12种的浓度随时间变化（各P 0.001）。与铁充足组相比，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以及磷酸肌酸/肌酸比值均升高（均P 0.02）。这些神经化学的改变表明，在围产期铁缺乏的静息能量状态，神经传递和髓鞘的持续变化。一个改变的神经化学档案的发展中海马可能是基础的一些认知缺陷观察人类婴儿围产期缺铁。

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.