Perinatal iron deficiency results in altered developmental expression of genes mediating energy metabolism and neuronal morphogenesis in hippocampus
Perinatal iron deficiency results in altered developmental expression of genes mediating energy metabolism and neuronal morphogenesis in hippocampus
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DOI：
10.1002/hipo.20307
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发表时间：
2007-01-01
期刊：
影响因子：
3.5
通讯作者：
Georgieff, Michael K.
中科院分区：
文献类型：
--
作者：
Carlson, Erik S.;Stead, John D. H.;Georgieff, Michael K.
人和大鼠海马在胎儿晚期、新生儿早期是铁摄取和利用的高峰期，对铁缺乏（ID）高度敏感。在此期间，ID改变了认知发育，其特征在于海马细胞生长和功能的独特的长期变化。这些变化背后的基本过程尚未完全理解。在这项研究中，ID诱导的25个基因表达的变化，涉及铁代谢，包括细胞生长和能量代谢，树突形态发生，和突触连接进行了评估，从出生后第7天（P）P65在海马。所有25个基因在I D期间（P7，15和30）表现出改变的表达; 10个在铁补充后P65发生变化。ID导致对海马神经元分化和可塑性至关重要的四种因子的蛋白质水平长期下降，包括CamKii alpha，Fkbp 1a（Fkbp 12），DIgh 4（PSD-95）和Vamp 1（Synaptobrevin-1）。ID改变了哺乳动物雷帕霉素靶（mTOR）途径和阿尔茨海默病病因学中涉及的基因网络中的基因表达。在胎儿晚期和出生后早期，ID改变了参与海马发育和功能的关键基因表达的水平和时间。这项研究为未来研究阐明铁在认知发育和功能中作用的分子机制提供了目标。(c)2007 Wiley-Liss，Inc.
The human and rat hippocampus is highly susceptible to iron deficiency (ID) during the late fetal, early neonatal time period which is a peak time of regulated brain iron uptake and utilization. ID during this period alters cognitive development and is characterized by distinctive, long-term changes in hippocampal cellular growth and function. The fundamental processes underlying these changes are not entirely understood. In this study, ID-induced changes in expression of 25 genes implicated in iron metabolism, including cell growth and energy metabolism, dendrite morphogenesis, and synaptic connectivity were assessed from postnatal day (P) 7 to P65 in hippocampus. All 25 genes showed altered expression during the period of I D (P7, 15, and 30); 10 had changes on P65 after iron repletion. ID caused long-term diminished protein levels of four factors critical for hippocampal neuron differentiation and plasticity, including CamKii alpha, Fkbp1a (Fkbpl2), DIgh4 (PSD-95), and Vamp1 (Synaptobrevin-1). I D altered gene expression in the mammalian target of rapamycin (mTOR) pathway and in a gene network implicated in Alzheimer disease etiology. ID during late fetal and early postnatal life alters the levels and timing of expression of critical genes involved in hippocampal development and function. The study provides targets for future studies in elucidating molecular mechanisms underpinning iron's role in cognitive development and function. (c) 2007 Wiley-Liss, Inc.