Manganese potentiates nitric oxide production by microglia.

Manganese toxicity has been associated with clinical symptoms of neurotoxicity which are similar to the symptoms observed in Parkinson's disease. Earlier 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 were associated with microglial activation. Results indicated that manganese significantly increased the bacterial lipopolysaccharide-induced nitric oxide production. This potent activity of manganese was not shared by other transition metals tested, including iron, cobalt, nickel, copper and zinc. Immunohistochemical staining and Western blot analysis indicated that manganese increased the cellular production of inducible nitric oxide synthase. Northern blot analysis indicated that manganese likely increased iNOS gene transcription since this agent increased the mRNA level of the inducible nitric oxide synthase. In contrast to other transition metals tested, manganese did not appear to be cytotoxic to microglial cells. These results suggested that manganese could induce sustained production of neurotoxic nitric oxide by activated microglial cells, which might cause detrimental consequences to surrounding neurons.