ToxSci Advance Access published online on October 23, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl139
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1 Department of Physiology & Pharmacology, Wake Forest University Health Sciences, Winston Salem, NC 27157
* To whom correspondence should be addressed. Manganese (Mn) neurotoxicity in adults can result in psychological and neurological disturbances similar to Parkinson's disease (PD), including extrapyramidal motor system defects and altered behaviors. Iron (Fe) deficiency is one of the most prevalent nutritional disorders in the world, affecting approximately 2 billion people, especially pregnant and lactating women, infants, toddlers, and adolescents. Fe deficiency can enhance brain Mn accumulation even in the absence of excess Mn in the environment or the diet. To assess the neurochemical interactions of dietary Fe deficiency and excess Mn during development, neonatal rats were exposed to either a control diet (CN), a low Fe diet (ID), or a low Fe diet supplemented with Mn (IDMn) via maternal milk during the lactation period (PN4-21). In PN21 pups, both the ID and IDMn diets produced changes in blood parameters characteristic of Fe deficiency: decreased hemoglobin (Hb) and plasma Fe; increased plasma transferrin (Tf) and total iron binding capacity (TIBC). Treated ID and IDMn dams also had decreased Hb throughout lactation and ID dams had decreased plasma Fe and increased TF and TIBC on PN21. Both ID and IDMn pups had decreased Fe and increased copper (Cu) brain levels; in addition, IDMn pups also had increased brain levels of several other essential metals including: Mn, chromium (Cr), zinc (Zn), cobalt (Co), aluminum (Al), molybdenum (Mo), and vanadium (V). Concurrent with altered concentrations of metals in the brain, transport proteins divalent metal transporter 1 (DMT-1) and transferrin receptor (TfR) were increased. No significant changes were determined for the neurotransmitters gamma aminobutyric acid (GABA) and glutamate. The results of this study confirm that there is homeostatic relationship among several essential metals in the brain and not simply between Fe and Mn.
Received August 29, 2006
Accepted October 14, 2006
Neurotoxicology
Iron Deficient and Manganese Supplemented Diets Alter Metals and Transporters in the Developing Rat Brain
Stephanie J. Garcia 1, Kristin Gellein 2, Tore Syversen 3, and Michael Aschner 4 *
2 Department of Chemistry, Norwegian University of Science and Technology, Trondheim, Norway
3 Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
4 Department of Pediatrics, Pharmacology, and the Kennedy Center, Vanderbilt University, Nashville, TN 37232-2495
Michael Aschner, E-mail: michael.aschner{at}vanderbilt.edu
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