Changes in dietary iron exacerbate regional brain manganese accumulation as determined by magnetic resonance imaging

Vanessa A. Fitsanakis, Na Zhang, Malcolm J. Avison, Keith M. Erikson, John C. Gore, Michael Aschner

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Manganese (Mn) is an essential metal required for normal homeostasis. Humans chronically exposed to high Mn levels, however, may exhibit psychomotor signs secondary to increased brain Mn. As Mn and iron (Fe) share several cellular membrane transporters, decreased Fe levels resulting from Fe deficiency or anemia lead to increased brain Mn deposition. Conversely, decreased Mn levels are associated with abnormal brain Fe accumulation. To reduce potential Mn toxicity resulting from brain Mn accumulation, we proposed that increased dietary Fe would attenuate brain Mn deposition. To test this hypothesis, three groups of Sprague-Dawley rats were injected weekly (14 weeks) with Mn (3 mg/kg) and fed normal Fe (TX), Fe-supplemented (FeS), or Fe-deficient (FeD) chow. Control (CN) rats received normal dietary Fe and saline injections. Using magnetic resonance imaging, rats were imaged biweekly for 14 weeks to qualitatively monitor brain Mn and Fe accumulation. Both FeS and FeD had greater brain Mn deposition than TX rats. By week 3, R1 values, which correlate with Mn deposition, were statistically significantly increased (p < 0.05) in brain stem, cerebellum, cortex, midbrain, and striatum compared with CN or TX animals. By week 14, R1 values for all brain regions in FeS and FeD animals were statistically significantly increased (p < 0.05). By the end of the study, similar results were obtained for R2 values, a marker of Fe accumulation. These data suggest that Fe supplementation does not effectively protect and may even exacerbate brain Mn accumulation in mammals subchronically exposed to Mn.

Original languageEnglish (US)
Pages (from-to)146-153
Number of pages8
JournalToxicological Sciences
Issue number1
StatePublished - Mar 2011
Externally publishedYes


  • Dietary iron
  • Magnetic resonance imaging
  • Manganese
  • Metal transport
  • Rat

ASJC Scopus subject areas

  • Toxicology


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