title: Quantitative proteomic analyses of cerebrospinal fluid using iTRAQ in a primate model of iron deficiency anemia.
abstract: Iron deficiency affects nearly 2 billion people worldwide, with pregnant women and young children being most severely impacted. Sustained anemia during the first year of life can cause cognitive, attention and motor deficits, which may persist despite iron supplementation. We conducted iTRAQ analyses on cerebrospinal fluid (CSF) from infant monkeys (Macaca mulatta) to identify differential protein expression associated with early iron deficiency. CSF was collected from 5 iron-sufficient and 8 iron-deficient anemic monkeys at weaning age (6-7 months) and again at 12-14 months. Despite consumption of iron-fortified food after weaning, which restored hematological indices into the normal range, expression of 5 proteins in the CSF remained altered. Most of the proteins identified are involved in neurite outgrowth, migration or synapse formation. The results reveal novel ways in which iron deficiency undermines brain growth and results in aberrant neuronal migration and connections. Taken together with gene expression data from rodent models of iron deficiency, we conclude that significant alterations in neuroconnectivity occur in the iron-deficient brain, which may persist even after resolution of the hematological anemia. The compromised brain infrastructure could account for observations of behavioral deficits in children during and after the period of anemia.
authors.affiliation: Penn State University College of Medicine, Hershey, PA, USA. smp11@psu.edu
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Patton
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Coe
authors.forename: Gabriele R
authors.initials: GR
authors.lastname: Lubach
authors.forename: James R
authors.initials: JR
authors.lastname: Connor
mesh_terms: D000367:Age Factors; D018798:Anemia, Iron-Deficiency / Q000134:cerebrospinal fluid* / Q000150:complications / Q000178:diet therapy / Q000196:embryology; D000818:Animals; D001925:Brain Damage, Chronic / Q000134:cerebrospinal fluid / Q000209:etiology; D002411:Cation Exchange Resins; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002852:Chromatography, Ion Exchange / Q000379:methods; D005260:Female; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D005527:Food, Fortified; D008253:Macaca mulatta; D008297:Male; D044342:Malnutrition / Q000503:physiopathology; D023421:Models, Animal; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid / Q000172:deficiency; D010446:Peptide Fragments / Q000032:analysis; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D014886:Weaning
chemical_list: D002411:Cation Exchange Resins; D002556:Cerebrospinal Fluid Proteins; D005296:Ferrous Compounds; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C020748:ferrous sulfate