Synthetic neuromelanin is toxic to dopaminergic cell cultures

• Published in: Journal of Neural Transmission Vol. 109; no. 5-6; pp. 651 - 661
• Main Authors: Nguyen, A, Gille, G, Moldzio, R, Hung, S-T, Rausch, W-D
• Format: Journal Article
• Language: English
• Published: Austria Springer Nature B.V 01-05-2002
• Subjects: 1-Methyl-4-phenylpyridinium - pharmacology; Animals; Cell Count; Cell Size - drug effects; Cells, Cultured; Dopamine - metabolism; dopaminergic cells; Dose-Response Relationship, Drug; Embryo, Mammalian; Ferric Compounds - pharmacology; Iron - metabolism; Melanins - administration & dosage; Melanins - chemical synthesis; Melanins - metabolism; Melanins - poisoning; Mesencephalon - cytology; Mesencephalon - drug effects; Mesencephalon - metabolism; Mice; neuromelanin; Neurons - drug effects; Neurons - pathology; Osmolar Concentration; Oxidation-Reduction
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s007020200054

In the present study, primary cultures of mesencephalic dopaminergic cells were exposed to synthetic dopamine neuromelanin (NM) for 48 hrs at concentrations of 0, 1, 10, 20, 50 and 100 microg NM/ml medium. Differently prepared synthetic NM with or without incorporated iron and NM oxidatively damaged by hydrogen peroxide were used. All NMs affected cellular structures e.g. as swelling of neural processes, rounding of cells, and occasional inclusion of neuromelanin particles. Cell numbers were uniformly and dose dependently reduced. Exposure to MPP(+) and ferric iron led to cytotoxic changes which could be further aggravated by oxidatively damaged NM, suggesting cytotoxicity of soluble compounds of NM in predamaged neurons.