Manganese potentiates nitric oxide production by microglia

Manganese toxicity has been associated with clinical symptoms of neurotoxic ity which are similar to the symptoms observed in Parkinson's disease. Earl ier reports indicated that reactive microglia was present in the substantia nigra of patients with Parkinson's disease. Using N9 microglial cells, the current study was designed to determine whether high levels of manganese w ere associated with microglial activation. Results indicated that manganese significantly increased the bacterial lipopolysaccharide-induced nitric ox ide production. This potent activity of manganese was not shared by other t ransition metals tested, including iron, cobalt, nickel, copper and zinc. I mmunohistochemical staining and Western blot analysis indicated that mangan ese increased the cellular production of inducible nitric oxide synthase. N orthern blot analysis indicated that manganese Likely increased iNOS gene t ranscription since this agent increased the mRNA level of the inducible nit ric oxide synthase. In contrast to other transition metals tested, manganes e did not appear to be cytotoxic to microglial cells. These results suggest ed that manganese could induce sustained production of neurotoxic nitric ox ide by activated microglial cells, which might cause detrimental consequenc es to surrounding neurons. (C) 1999 Elsevier Science B.V. All rights reserv ed.