Perinatal iron deficiency results in altered developmental expression of genes mediating energy metabolism and neuronal morphogenesis in hippocampus

被引:101
作者
Carlson, Erik S.
Stead, John D. H.
Neal, Charles R.
Petryk, Anna
Georgieff, Michael K.
机构
[1] Univ Minnesota, Med Sci Training Program, Minneapolis, MN USA
[2] Univ Minnesota, Grad Program Neurosci, Minneapolis, MN 55455 USA
[3] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA
[4] Univ Minnesota, Ctr Neurobehav Dev, Minneapolis, MN USA
[5] Carleton Univ, Inst Neurosci, Ottawa, ON K1S 5B6, Canada
[6] Univ Hawaii, Dept Pediat, Honolulu, HI 96822 USA
[7] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA
关键词
neonatal; microarray; dendrite development; synaptogenesis; developmental disorders;
D O I
10.1002/hipo.20307
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:679 / 691
页数:13
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