title: Iron deficiency alters expression of genes implicated in Alzheimer disease pathogenesis.
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.
authors: Department of Pediatrics, University of Minnesota School of Medicine, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
authors: Erik S
authors: ES
authors: Carlson
authors: Rhamy
authors: R
authors: Magid
authors: Anna
authors: A
authors: Petryk
authors: Michael K
authors: MK
authors: Georgieff
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000704:Analysis of Variance; D018798:Anemia, Iron-Deficiency / Q000150:complications*; D000818:Animals; D000831:Animals, Newborn; D027682:Cation Transport Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D046228:Microarray Analysis / Q000379:methods; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D016229:Amyloid beta-Peptides; D027682:Cation Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000099173:Natural Resistance-associated Macrophage Protein 1