Manganese Exposure Alters the Expression of N-Methyl-D-aspartate Receptor Subunit mRNAs and Proteins in Rat Striatum

Manganese is one of the ubiquitous environmental pollutants that can induce an indirect excitotoxicity caused by altered glutamate (Glu) metabolism. The present study has been carried out to investigate the effect of Mn on the expression of N-methyl-D-aspartate receptor (NR) subunit mRNAs and proteins in rat striatum when rats were in manganism. The rats were divided randomly into four groups of six males and six females each: control group (group 1) and 8, 40, and 200 mu mol/kg Mn-treated groups (groups 2-4). The control group rats were subcutaneously (s.c.) injected with normal saline. Manganese-treated rats were s.c. injected with respectively 8,40, and 200 mu mol/kg of MnCl2 center dot 6H(2)O in normal saline. The administration of MnCl2 center dot 6H(2)O for 4 weeks significantly increased Mn concentration in the striatum. With the increase in administered MnCl2 dosage, Glu concentration and cell apoptosis rate increased significantly. The relative intensity of NR2A mRNA decreased significantly in 8 mu mol/kg Mn-treated rats. However, relative intensities of NR1 and NR2B mRNAs decreased significantly in 40 mu mol/kg Mn-treated rats. Similarly, the relative intensity of NR2A protein showed a significant decrease in 40 I.Lmollkg Mn-treated rats whereas those of NR1 and NR2B decreased significantly in 200 mu mol/kg Mn-treated rats. Therefore, the expression of NR2A mRNA and protein were much more sensitive to Mn than that of NR1 and NR2B. In conclusion, the results suggested that Mn induced nerve cell damage by increasing extracellular Glu level and altered expression of NR subunit mRNAs and proteins in rat striatum. (C) 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:1-9, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10:1002/jbt.20306