Iron deficiency alters expression of genes implicated in Alzheimer disease pathogenesis

Erik S. Carlson, Rhamy Magid, Anna Petryk, Michael K Georgieff

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Neonatal brain iron deficiency occurs after insufficient maternal dietary iron intake, maternal hypertension, and maternal diabetes mellitus and results in short and long-term neurologic and behavioral deficits. Early iron deficiency affects the genomic profile of the developing hippocampus that persists despite iron repletion. The purpose of the present study was threefold: 1) quantitative PCR confirmation of our previous microarray results, demonstrating upregulation of a network of genes leading to beta-amyloid production and implicated in Alzheimer disease etiology in iron-deficient anemic rat pups at the time of hippocampal differentiation; 2) investigation of the potential contributions of iron deficiency anemia and iron treatment to this differential gene expression in the hippocampus; and 3) investigation of these genes over a developmental time course in a mouse model where iron deficiency is limited to hippocampus, is not accompanied by anemia and is not repletable. Quantitative PCR confirmed altered regulation in 6 of 7 Alzheimer-related genes (Apbb1, C1qa, Clu, App, Cst3, Fn1, Htatip) in iron-deficient rats relative to iron-sufficient controls at P15. Comparison of untreated to treated iron-deficient animals at this age suggested the strong role of iron deficiency, not treatment, in the upregulation of this gene network. The non-anemic hippocampal iron-deficient mouse demonstrated upregulation of all 7 genes in this pathway from P5 to P25. Our results suggest a role for neonatal iron deficiency in dysregulation of genes that may set the stage for long-term neurodegenerative disease and that this may occur through a histone modification mechanism.

Original languageEnglish (US)
Pages (from-to)75-83
Number of pages9
JournalBrain Research
Volume1237
DOIs
StatePublished - Oct 27 2008

Keywords

  • Alzheimer Disease
  • Amyloid precursor protein
  • Genes
  • Hippocampus
  • Iron deficiency

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