ToxSci Advance Access originally published online on January 30, 2008
Toxicological Sciences 2008 103(1):116-124; doi:10.1093/toxsci/kfn019
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Measuring Brain Manganese and Iron Accumulation in Rats following 14 Weeks of Low-Dose Manganese Treatment Using Atomic Absorption Spectroscopy and Magnetic Resonance Imaging
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* Department of Biology, King College, Bristol, Tennessee 37620
Vanderbilt University Institute of Imaging Science and Department of Physics & Astronomy, Vanderbilt University, Nashville, Tennessee 37232
Department of Nutrition, University of North Carolina Greensboro, Greensboro, North Carolina 27402
Departments of Radiology & Radiological Sciences, Biomedical Engineering, Molecular Physiology & Biophysics, Vanderbilt University, Nashville, Tennessee 37232
¶ Vanderbilt University Medical Center, Departments of Pharmacology and Pediatrics, Center for Molecular Neuroscience and Center in Molecular Toxicology, Nashville, Tennessee 37232
1 To whom correspondence should be addressed at Vanderbilt University Medical Center, 6110 MRB-III, 1161 21st Avenue South, Nashville, TN 37232-2495. Fax: (615) 322-6541. E-mail: Michael.Aschner{at}vanderbilt.edu.
Received December 20, 2007; accepted January 17, 2008
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Abstract |
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Chronic exposure to manganese (Mn) may lead to a movement disorder due to preferential Mn accumulation in the globus pallidus and other basal ganglia nuclei. Iron (Fe) deficiency also results in increased brain Mn levels, as well as dysregulation of other trace metals. The relationship between Mn and Fe transport has been attributed to the fact that both metals can be transported via the same molecular mechanisms. It is not known, however, whether brain Mn distribution patterns due to increased Mn exposure vs. Fe deficiency are the same, or whether Fe supplementation would reverse or inhibit Mn deposition. To address these questions, we utilized four distinct experimental populations. Three separate groups of male Sprague–Dawley rats on different diets (control diet [MnT], Fe deficient [FeD], or Fe supplemented [FeS]) were given weekly intravenous Mn injections (3 mg Mn/kg body mass) for 14 weeks, whereas control (CN) rats were fed the control diet and received sterile saline injections. At the conclusion of the study, both blood and brain Mn and Fe levels were determined by atomic absorption spectroscopy and magnetic resonance imaging. The data indicate that changes in dietary Fe levels (either increased or decreased) result in regionally specific increases in brain Mn levels compared with CN or MnT animals. Furthermore, there was no difference in either Fe or Mn accumulation between FeS or FeD animals. These data suggest that dietary Fe manipulation, whether increased or decreased, may contribute to brain Mn deposition in populations vulnerable to increased Mn exposure.
Key Words: Iron deficiency (ID); iron supplementation; brain Mn accumulation; MMT; MRI.