Manganese inhalation by rhesus monkeys is associated with brain regional changes in biomarkers of oxidative stress including glutamate transporters

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/m 3 ha