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Nutritional Neurosciences

Perinatal Iron Deficiency Alters the Neurochemical Profile of the Developing Rat Hippocampus^1,2

Raghavendra Rao^*,,3, Ivan Tkac^,, Elise L. Townsend^**,, Rolf Gruetter^,, and Michael K. Georgieff^*,**,

Departments of ^* Pediatrics and Radiology, ^** Institute of Child Development, Center for Magnetic Resonance Research and Center for Neurobehavioral Development, University of Minnesota, Minneapolis, MN 55455

³To whom correspondence and reprint requests should be addressed. E-mail: raoxx017{at}umn.edu.

Cognitive deficits in human infants at risk for gestationally acquired perinatal iron deficiency suggest involvement of the developing hippocampus. To understand the plausible biological explanations for hippocampal injury in perinatal iron deficiency, a neurochemical profile of 16 metabolites in the iron-deficient rat hippocampus was evaluated longitudinally by ¹H NMR spectroscopy at 9.4 T. Metabolites were quantified from an 11–24 µL volume centered in the hippocampus in 18 iron-deficient and 16 iron-sufficient rats on postnatal day (PD) 7, PD10, PD14, PD21 and PD28. Perinatal iron deficiency was induced by feeding the pregnant dam an iron-deficient diet from gestational d 3 to PD7. The brain iron concentration of the iron-deficient group was 60% lower on PD7 and 19% lower on PD28 (P < 0.001 each). The concentration of 12 of the 16 measured metabolites changed over time between PD7 and PD28 in both groups (P < 0.001 each). Compared with the iron-sufficient group, phosphocreatine, glutamate, N-acetylaspartate, aspartate, -aminobutyric acid, phosphorylethanolamine and taurine concentrations, and the phosphocreatine/creatine ratio were elevated in the iron-deficient group (P < 0.02 each). These neurochemical alterations suggest persistent changes in resting energy status, neurotransmission and myelination in perinatal iron deficiency. An altered neurochemical profile of the developing hippocampus may underlie some of the cognitive deficits observed in human infants with perinatal iron deficiency.

KEY WORDS: • hippocampus • iron • neurochemical profile • NMR spectroscopy • perinatal iron deficiency

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