Neurotoxicity Research

, 15:167 | Cite as

A Chronic Iron-Deficient/High-Manganese Diet in Rodents Results in Increased Brain Oxidative Stress and Behavioral Deficits in the Morris Water Maze

  • Vanessa A. Fitsanakis
  • Kimberly N. Thompson
  • Sarah E. Deery
  • Dejan Milatovic
  • Zak K. Shihabi
  • Keith M. Erikson
  • Russell W. Brown
  • Michael AschnerEmail author


Iron deficiency (ID) is especially common in pregnant women and may even persist following childbirth. This is of concern in light of reports demonstrating that ID may be sufficient to produce homeostatic dysregulation of other metals, including manganese (Mn). These results are particularly important considering the potential introduction of the Mn-containing gas additive, methyl cyclopentadienyl manganese tricarbonyl (MMT), in various countries around the world. In order to model this potentially vulnerable population, we fed female rats fed either control (35 mg Fe/kg chow; 10 mg Mn/kg chow) or low iron/high-manganese (IDMn; 3.5 mg Fe/kg chow; 100 mg Mn/kg chow) diet, and examined whether these changes had any long-term behavioral effects on the animals’ spatial abilities, as tested by the Morris water maze (MWM). We also analyzed behavioral performance on auditory sensorimotor gating utilizing prepulse inhibition (PPI), which may be related to overall cognitive performance. Furthermore, brain and blood metal levels were assessed, as well as regional brain isoprostane production. We found that treated animals were slightly ID, with statistically significant increases in both iron (Fe) and Mn in the hippocampus, but statistically significantly less Fe in the cerebellum. Additionally, isoprostane levels, markers of oxidative stress, were increased in the brain stem of IDMn animals. Although treated animals were indistinguishable from controls in the PPI experiments, they performed less well than controls in the MWM. Taken together, our data suggest that vulnerable ID populations exposed to high levels of Mn may indeed be at risk of potentially dangerous alterations in brain metal levels which could also lead to behavioral deficits.


Iron deficiency Manganese Morris water maze MMT Prepulse inhibition (PPI) Isoprostanes 


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Vanessa A. Fitsanakis
    • 1
  • Kimberly N. Thompson
    • 2
  • Sarah E. Deery
    • 3
  • Dejan Milatovic
    • 3
  • Zak K. Shihabi
    • 4
  • Keith M. Erikson
    • 5
  • Russell W. Brown
    • 2
    • 6
  • Michael Aschner
    • 3
    • 7
    Email author
  1. 1.Department of BiologyKing CollegeBristolUSA
  2. 2.Department of PsychologyEast Tennessee State UniversityJohnson CityUSA
  3. 3.Department of PediatricsVanderbilt University Medical CenterNashvilleUSA
  4. 4.Department of PathologyWake Forest University School of MedicineWinston-SalemUSA
  5. 5.Department of NutritionUniversity of North Carolina GreensboroGreensboroUSA
  6. 6.Department of Anatomy and Cell Biology, Quillen College of MedicineEast Tennessee State UniversityJohnson CityUSA
  7. 7.Department of Pharmacology, Center for Molecular NeuroscienceVanderbilt University Medical CenterNashvilleUSA

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