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

Authors

  • Erik S. Carlson,

    1. Medical Scientist Training Program, University of Minnesota, Minneapolis, Minnesota
    2. Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota
    3. Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
    4. Center for Neurobehavioral Development, University of Minnesota, Minneapolis, Minnesota
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  • John D.H. Stead,

    1. Institute of Neuroscience, Carleton University, Ottawa, Ontario, Canada
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  • Charles R. Neal,

    1. Department of Pediatrics, University of Hawaii, Honolulu, Hawaii
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  • Anna Petryk,

    1. Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
    2. Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota
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  • Michael K. Georgieff

    Corresponding author
    1. Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota
    2. Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
    3. Center for Neurobehavioral Development, University of Minnesota, Minneapolis, Minnesota
    • MMC 39 D-136 Mayo, 420 Delaware Street SE, Minneapolis, MN 55455, USA
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Abstract

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 ID (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 CamKIIα, Fkbp1a (Fkbp12), Dlgh4 (PSD-95), and Vamp1 (Synaptobrevin-1). ID 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. © 2007 Wiley-Liss, Inc.

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