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Metabolomic Analysis of Cerebrospinal Fluid Indicates Iron Deficiency Compromises Cerebral Energy Metabolism in the Infant Monkey

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Abstract

Iron deficiency anemia affects many pregnant women and young infants worldwide. The health impact is significant, given iron’s known role in many body functions, including oxidative and lipid metabolism, protein synthesis and brain neurochemistry. The following research determined if 1H NMR spectroscopy-based metabolomic analysis of cerebrospinal fluid (CSF) could detect the adverse influence of early life iron deficiency on the central nervous system. Using a controlled dietary model in 43 infant primates, distinct differences were found in spectra acquired at 600 MHz from the CSF of anemic monkeys. Three metabolite ratios, citrate/pyruvate, citrate/lactate and pyruvate/glutamine ratios, differed significantly in the iron deficient infant and then normalized following the consumption of dietary iron and improvement of clinical indices of anemia in the heme compartment. This distinctive metabolomic profile associated with anemia in the young infant indicates that CSF can be employed to track the neurological effects of iron deficiency and benefits of iron supplementation.

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Acknowledgments

This research was supported in part by awards from the National Institute of Health/National Institute of Child Health and Development (R01 HD057064, P01 HD39386) and a Grand Challenges Explorations award from the Bill and Melinda Gates Foundation (Opp1046203). We are grateful to Dr. Stephen Provencher for assistance with LC Model analysis of CSF spectra.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Neonatology, University of Minnesota, Mayo Mail Code 391, 420 Delaware Street, SE, Minneapolis, MN, 55455, USA

    Raghavendra Rao, Kathleen Ennis & Michael K. Georgieff

  2. Center for Neurobehavioral Development, University of Minnesota, Minneapolis, MN, 55455, USA

    Raghavendra Rao & Michael K. Georgieff

  3. Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, 55455, USA

    Gulin Oz

  4. Harlow Center for Biological Psychology, University of Wisconsin, Madison, WI, 53715, USA

    Gabriele R. Lubach & Christopher L. Coe

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  1. Raghavendra Rao
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  2. Kathleen Ennis
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  4. Gabriele R. Lubach
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  5. Michael K. Georgieff
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Correspondence to Raghavendra Rao.

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Rao, R., Ennis, K., Oz, G. et al. Metabolomic Analysis of Cerebrospinal Fluid Indicates Iron Deficiency Compromises Cerebral Energy Metabolism in the Infant Monkey. Neurochem Res 38, 573–580 (2013). https://doi.org/10.1007/s11064-012-0950-7

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  • DOI: https://doi.org/10.1007/s11064-012-0950-7

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