Iron supplementation dose for perinatal iron deficiency differentially alters the neurochemistry of the frontal cortex and hippocampus in adult rats

Raghavendra Rao, Ivan Tkac, Erica L. Unger, Kathleen Ennis, Amy Hurst, Timothy Schallert, James Connor, Barbara Felt, Michael K. Georgieff

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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.Conclusion: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.

Original languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalPediatric Research
Volume73
Issue number1
DOIs
StatePublished - Jan 2013

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