title: CSF proteomic analysis reveals persistent iron deficiency-induced alterations in non-human primate infants.
abstract: Iron deficiency (ID) anemia during infancy results in long-term neurological consequences, yet the mediating mechanisms remain unclear. Infant monkeys often become naturally anemic during the first 6 months of life, presenting an opportunity to determine the effect of developmental iron deficiency. After weaning, animals were chosen randomly for supplementation with oral iron or, fed a standard commercial chow diet. The control group was never iron deficient. ID anemia was corrected by 12 months in both groups, as indicated by hematological parameters. CSF was collected for proteomic analysis at 12 months of age to assess the impact of developmental ID on the brain. The CSF proteome for both formerly iron deficient groups was similar and revealed 12 proteins with expression levels altered at least twofold. These proteins were identified by matrix assisted laser desorption ionization time-of-flight spectrometry and included prostaglandin D synthase, olfactory receptors and glial fibrillary acidic protein. Thus the proteomic analysis reveals a persistent effect of ID and provides insights into reports of disturbed sleep, hypomyelination and other behavioral alterations associated with ID. Furthermore, alterations in the CSF proteome despite normal hematologic parameters indicate that there is a hierarchical system that prioritizes repletion of red cell mass at the expense of the brain.
authors.affiliation: Department of Neurosurgery, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA.
authors.forename: Ramaz N
authors.initials: RN
authors.lastname: Geguchadze
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Coe
authors.forename: Gabriele R
authors.initials: GR
authors.lastname: Lubach
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Clardy
authors.forename: John L
authors.initials: JL
authors.lastname: Beard
authors.forename: James R
authors.initials: JR
authors.lastname: Connor
mesh_terms: D000367:Age Factors; D018798:Anemia, Iron-Deficiency / Q000134:cerebrospinal fluid* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000502:physiology; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid; D019746:Intramolecular Oxidoreductases / Q000134:cerebrospinal fluid; D054834:Lipocalins / Q000134:cerebrospinal fluid; D008253:Macaca mulatta; D040081:Protein Array Analysis; D040901:Proteomics / Q000379:methods*; D011897:Random Allocation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D005904:Glial Fibrillary Acidic Protein; D054834:Lipocalins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase