Hippocampus specific iron deficiency alters competition and cooperation between developing memory systems

Erik S. Carlson, Stephanie J.B. Fretham, Erica Unger, Michael B O'Connor, Anna Petryk, Timothy Schallert, Raghu Rao, Ivan Tkac, Michael K Georgieff

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Iron deficiency (ID) is the most common gestational micronutrient deficiency in the world, targets the fetal hippocampus and striatum and results in long-term behavioral abnormalities. These structures primarily mediate spatial and procedural memory, respectively, in the rodent but have interconnections that result in competition or cooperation during cognitive tasks. We determined whether ID-induced impairment of one alters the function of the other by genetically inducing a 40% reduction of hippocampus iron content in late fetal life in mice and measuring dorsal striatal gene expression and metabolism and the behavioral balance between the two memory systems in adulthood. Slc11a2hipp/hipp mice had similar striatum iron content, but 18% lower glucose and 44% lower lactate levels, a 30% higher phosphocreatine:creatine ratio, and reduced iron transporter gene expression compared to wild type (WT) littermates, implying reduced striatal metabolic function. Slc11a2hipp/hipp mice had longer mean escape times on a cued task paradigm implying impaired procedural memory. Nevertheless, when hippocampal and striatal memory systems were placed in competition using a Morris Water Maze task that alternates spatial navigation and visual cued responses during training, and forces a choice between hippocampal and striatal strategies during probe trials, Slc11a2hipp/hipp mice used the hippocampus-dependent response less often (25%) and the visual cued response more often (75%) compared to WT littermates that used both strategies approximately equally. Hippocampal ID not only reduces spatial recognition memory performance but also affects systems that support procedural memory, suggesting an altered balance between memory systems.

Original languageEnglish (US)
Pages (from-to)133-143
Number of pages11
JournalJournal of neurodevelopmental disorders
Volume2
Issue number3
DOIs
StatePublished - 2010

Bibliographical note

Funding Information:
Acknowledgements Supported by the grants: NIH R21 HD054490, NIH R01 HD29421, Minnesota Medical Foundation at the University of Minnesota, Vikings Children’s Fund at the University of Minnesota to M.K.G.; NIH: NINDS Individual Kirschstein-NRSA F31 NS047876, a seed grant from the American Medical Association Foundation, and the Dr. Warren J. Warwick and Henrietta Holm Warwick Fellowship Award to E.S.C; and NIH P-01 HD039386 awarded to M.K.G., T.S, R.R. and E.U; NIH grants P41 RR008079, P30 NS057091 and the Keck Foundation to I.T.

Keywords

  • DMT1, Slc11a2, Nuclear magnetic resonance spectroscopy
  • Hippocampus
  • Iron deficiency
  • Memory systems
  • Morris water maze
  • Procedural memory
  • Spatial memory
  • Striatum

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