Korean J Prev Med.  1999 Dec;32(4):459-466.

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

• Shin DH
• Jung YW
• Bae JH
• Song DK
• Park WK
• Ko BH
• Kim DH

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.

Keyword

Manganese(Mn); Nitric oxide(NO); Nitric oxide synthase(NOS); Neurotoxicity; Neurons

MeSH Terms

Animals
Basal Ganglia*
Cell Culture Techniques
Equidae
Fluorescent Antibody Technique
Manganese*
Microscopy, Confocal
Neurons*
Nitric Oxide
Nitroarginine
Rats
Receptors, N-Methyl-D-Aspartate
Manganese
Nitric Oxide
Nitroarginine
Receptors, N-Methyl-D-Aspartate