Article

Journal of Neurodevelopmental Disorders

, Volume 2, Issue 3, pp 133-143

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Erik S. CarlsonAffiliated withMedical Scientist Training Program, University of Minnesota Medical SchoolGraduate Program in Neuroscience, University of Minnesota Medical SchoolPediatrics, University of Minnesota Medical SchoolCenter for Neurobehavioral Development, Graduate Program in Neuroscience, University of Minnesota Medical School
  • , Stephanie J. B. FrethamAffiliated withGraduate Program in Neuroscience, University of Minnesota Medical SchoolPediatrics, University of Minnesota Medical SchoolCenter for Neurobehavioral Development, Graduate Program in Neuroscience, University of Minnesota Medical School
  • , Erica UngerAffiliated withDepartment of Nutritional Sciences, Pennsylvania State University
  • , Michael O’ConnorAffiliated withGenetics, Cell Biology and Development, University of Minnesota Medical SchoolHoward Hughes Medical Institute
  • , Anna PetrykAffiliated withPediatrics, University of Minnesota Medical SchoolGenetics, Cell Biology and Development, University of Minnesota Medical School
  • , Timothy SchallertAffiliated withMedical Scientist Training Program, University of Minnesota Medical SchoolDepartments of Psychology, University of Texas at AustinDepartments of Neurobiology, University of Texas at AustinDepartment of Neurosurgery and Development, University of MichiganCenter for Human Growth and Development, University of Michigan
  • , Raghavendra RaoAffiliated withGraduate Program in Neuroscience, University of Minnesota Medical SchoolPediatrics, University of Minnesota Medical SchoolCenter for Neurobehavioral Development, Graduate Program in Neuroscience, University of Minnesota Medical SchoolCenter for Magnetic Resonance Research, Graduate Program in Neuroscience, University of Minnesota Medical School
  • , Ivan TkacAffiliated withCenter for Magnetic Resonance Research, Graduate Program in Neuroscience, University of Minnesota Medical School
  • , Michael K. GeorgieffAffiliated withGraduate Program in Neuroscience, University of Minnesota Medical SchoolPediatrics, University of Minnesota Medical SchoolCenter for Neurobehavioral Development, Graduate Program in Neuroscience, University of Minnesota Medical School Email author 

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. Slc11a2 hipp/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. Slc11a2 hipp/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, Slc11a2 hipp/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.

Keywords

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