ToxSci Advance Access originally published online on March 7, 2007
Toxicological Sciences 2007 97(2):459-466; doi:10.1093/toxsci/kfm044
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Manganese Inhalation by Rhesus Monkeys is Associated with Brain Regional Changes in Biomarkers of Neurotoxicity
* Department of Nutrition, University of North Carolina Greensboro, Greensboro, North Carolina 27402-6170
CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709
Department of Pharmacology, Wayne State University, Detroit, Michigan 48202
Departments of Pediatrics, Pharmacology, and the Kennedy Center for Research on Human Development, Vanderbilt University Medical Center, Nashville, Tennessee 37235
1 To whom correspondence should be addressed. Fax: (336) 334-4129. E-mail: kmerikso{at}uncg.edu.
Received January 7, 2007; accepted March 3, 2007
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Abstract |
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The purpose of this study was to evaluate biochemical markers of neurotoxicity following subchronic manganese sulfate (MnSO4) inhalation. Juvenile rhesus monkeys were exposed to MnSO4 at 0, 0.06, 0.3, or 1.5 mg Mn/m3 for 65 days. Glutamine synthetase (GS), glutamate transporters (glutamate transporter-1 [GLT-1] and glutamate/aspartate transporter [GLAST]) and tyrosine hydroxylase (TH) protein levels, metallothionein (MT), GLT-1, GLAST, TH and GS mRNA levels, and total glutathione (GSH) levels were assessed in known targets (caudate, globus pallidus, putamen) as well as the cerebellum, frontal cortex, and olfactory cortex. All MnSO4-exposed monkeys had decreased pallidal GS protein, decreased caudate GLT-1 mRNA, decreased pallidal GLAST protein, and increased olfactory cortical TH mRNA levels. Monkeys exposed to MnSO4 at 0.06 or 0.3 mg Mn/m3 had significantly increased pallidal mRNA levels for GLT-1, GLAST, and TH. Monkeys exposed to MnSO4 at 
0.3 mg Mn/m3 had several alterations including decreased frontal cortical MT mRNA, decreased caudate, globus pallidus, olfactory cortex, and cerebellum GLT-1 protein, decreased olfactory cortex and cerebellum GLAST protein, increased cerebellar GLAST mRNA, and decreased pallidal TH protein levels. Lastly, GSH levels were significantly increased in the frontal cortex and decreased in the caudate of monkeys exposed to the 1.5-mg Mn/m3 compared to the controls. Overall, as in our previous studies, we observed that increased Mn concentrations due to airborne Mn exposure differentially affects biomarkers in each brain region (e.g., GSH was increased in the frontal cortex and decreased in the caudate despite two- to threefold increases in Mn concentrations in these regions).
Key Words: monkey; manganese; brain; glutamate transporters; glutathione; glutamine synthetase.
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