title: Iron supplementation dose for perinatal iron deficiency differentially alters the neurochemistry of the frontal cortex and hippocampus in adult rats.
abstract: BACKGROUND
  Long-term prefrontal cortex (PFC)- and hippocampus-based cognitive deficits are the sequelae of perinatal iron deficiency, despite iron supplementation starting in the newborn period. Whether high-dose iron supplementation prevents these deficits is yet to be determined.
  
  
  METHODS
  Perinatal iron deficiency was induced in rat pups using a low-iron (3 mg/kg diet) diet during gestation until postnatal day (P)8. Iron was supplemented using a standard (40 mg/kg diet) or a 10-fold higher (400 mg/kg diet) iron-containing diet until P21. PFC and hippocampal neurochemistry was determined using in vivo (1)H nuclear magnetic resonance (NMR) spectroscopy at 9.4 Tesla on P90.
  
  
  RESULTS
  Both standard and 10-fold higher iron supplementation doses corrected anemia and brain iron deficiency by P21. The neurochemical profile of the PFC in both supplementation groups was comparable with the control group. In the hippocampus, standard-dose iron supplementation resulted in lower concentrations of N-acetylaspartate (NAA) and phosphoethanolamine (PE) and higher concentrations of N-acetylaspartylglutamate (NAAG) and glycerophosphocholine + phosphocholine (GPC + PC). High-dose iron supplementation resulted in lower PE and higher GPC + PC concentrations.
  
  
  CONCLUSIONS
  The iron supplementation dose for perinatal iron deficiency differentially alters the neurochemical profile of the PFC and hippocampus in adults. The neurochemical changes suggest altered glutamatergic neurotransmission, hypomyelination, and abnormal phospholipid metabolism in the formerly iron-deficient (FID) hippocampus.
authors.affiliation: Department of Pediatrics, Neonatology Division, University of Minnesota, Minneapolis, MN, USA. raghurao@umn.edu
authors.forename: Raghavendra
authors.initials: R
authors.lastname: Rao
authors.forename: Ivan
authors.initials: I
authors.lastname: Tkac
authors.forename: Erica L
authors.initials: EL
authors.lastname: Unger
authors.forename: Kathleen
authors.initials: K
authors.lastname: Ennis
authors.forename: Amy
authors.initials: A
authors.lastname: Hurst
authors.forename: Timothy
authors.initials: T
authors.lastname: Schallert
authors.forename: James
authors.initials: J
authors.lastname: Connor
authors.forename: Barbara
authors.initials: B
authors.lastname: Felt
authors.forename: Michael K
authors.initials: MK
authors.lastname: Georgieff
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000150:complications*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control*; D019587:Dietary Supplements; D004151:Dipeptides / Q000032:analysis; D004983:Ethanolamines / Q000032:analysis; D005625:Frontal Lobe / Q000737:chemistry*; D006624:Hippocampus / Q000737:chemistry*; D007501:Iron / Q000378:metabolism / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D010767:Phosphorylcholine / Q000032:analysis; D051381:Rats
chemical_list: D004151:Dipeptides; D004983:Ethanolamines; D010767:Phosphorylcholine; C027172:isospaglumic acid; D001224:Aspartic Acid; C005448:phosphorylethanolamine; C000179:N-acetylaspartate; D007501:Iron