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 micromol/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 micromol/kg of MnCl(2) . 6H(2)O in normal saline. The administration of MnCl(2) . 6H(2)O for 4 weeks significantly increased Mn concentration in the striatum. With the increase in administered MnCl(2) dosage, Glu concentration and cell apoptosis rate increased significantly. The relative intensity of NR2A mRNA decreased significantly in 8 micromol/kg Mn-treated rats. However, relative intensities of NR1 and NR2B mRNAs decreased significantly in 40 micromol/kg Mn-treated rats. Similarly, the relative intensity of NR2A protein showed a significant decrease in 40 micromol/kg Mn-treated rats whereas those of NR1 and NR2B decreased significantly in 200 micromol/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.
Xu
Bin
B
Department of Environmental Health, School of Public Health, China Medical University, North 2nd Road 92, Heping ward, Shenyang, Liaoning 110001, People's Republic of China.
Xu
Zhao-Fa
ZF
Deng
Yu
Y
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002712:Chlorides / Q000008:administration & dosage; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D018698:Glutamic Acid / Q000032:analysis; D020260:Heavy Metal Poisoning, Nervous System / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity*; D017895:Manganese Compounds / Q000008:administration & dosage; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
D017304:Annexin A5; D002712:Chlorides; D004785:Environmental Pollutants; D017895:Manganese Compounds; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D008345:Manganese; C025340:manganese chloride