Nitric Oxide-Mediated Cytotoxicity of Manganese in Basal Ganglia Neuronal Cells / 예방의학회지

ABSTRACT

OBJECTIVES: We have investigated to manifest whether manganese-induced neurotoxicity is mediated by nitric oxide(NO) in the rat primary neuronal cultures and assess the effect of Mn2+ on the N-methyl-D aspartate(NMDA) receptors. METHODS: We have used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay to examine the effect of cytotoxicity of MnCl2 in neuronal cells . NO production was determined by measuring nirites, a stable oxidation product of NO. The neurons in the rat that contains neuronal nitric oxide synthase(nNOS) were examined by immunofluorescence and confocal microscopy. The effects of Mn2+ on the NMDA receptors was assesed by the whole cell voltage clamp technique. RESULTS: We showed that the NO release and NOS expression were increased with 500uM MnCl2 treatment and an NOS inhibitors, NG-nitro-L-arginine , prevented neurotoxicity elicited by manganese. In the electrophysiological study, Mn2+ does not block or activate the NMDA receptors and not pass through the NMDA receptors in a neurons of basal ganglia. CONCLUSIONS: It is concluded that manganese neurotoxicity in basal ganglia was partially mediated by nitric oxide in the cell culture model.