ToxSci Advance Access originally published online on May 16, 2006
Toxicological Sciences 2006 92(2):516-525; doi:10.1093/toxsci/kfl017
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A Manganese-Enhanced Diet Alters Brain Metals and Transporters in the Developing Rat
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* Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157; Department of Chemistry, Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway; and Departments of Pediatrics, Pharmacology, and The Kennedy Center, Vanderbilt University, Nashville, Tennessee 37232-2495
Received March 16, 2006; accepted May 8, 2006
Manganese (Mn) neurotoxicity in adults can result in psychological and neurological disturbances similar to Parkinson's disease, including extrapyramidal motor system defects and altered behaviors. However, virtually nothing is known regarding excess Mn accumulation during central nervous system development. Developing rats were exposed to a diet high in Mn via maternal milk during lactation (PN4-21). The high Mn diet resulted in changes in hematological parameters similar to those seen with iron (Fe) deficiency in dams (decreased plasma Fe; increased plasma transferrin [Tf]) and pups (decreased hemoglobin [Hb] and plasma Fe; increased plasma Tf and total iron binding capacity). Mn-exposed pups showed an increase in brain Mn, chromium, and zinc concurrent with a decrease in brain Fe. In conjunction with the altered transport and distribution of essential metals within the brain, there was enhanced protein expression of the divalent metal transporter-1 (DMT-1) and transferrin receptor (TfR) overall in the brain; there was a general increase in each region analyzed (cerebellum, cortex, hippocampus, midbrain, and striatum). Neurochemical changes were observed as an increase in 
-aminobutyric acid (GABA) and the ratio of GABA to glutamate, indicating enhanced inhibitory transmission in the brain. The results of this study demonstrate that developing rats undergo alterations in the transport and distribution of essential metals translating to neurochemical perturbations after maternal exposure to a diet supplemented with excess levels of Mn.
Key Words: manganese; iron deficiency; brain; development; rat.
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