LPS mediated injury to oligodendrocytes is mediated by the activation of nNOS: relevance to human demyelinating disease.

Loss of oligodendrocytes and the destruction of myelin form the core features of inflammatory demyelinating disease. Although many of the inflammatory and cellular mediators of tissue injury are known, recent studies have suggested an important role for nitric oxide NO and other reactive nitrogen species in oligodendrocyte injury. The human transformed oligodendrocyte cell line, MO3.13 cells, express Toll like receptor genes (TLR) genes and are activated by lipopolysaccharide (LPS). We determined the activation and consequences of neuronal nitric oxide synthase (nNOS) following stimulation with LPS in the MO3.13 cell line. Our studies show that MO3.13 cells induce nNOS following stimulation with LPS. Most importantly, these studies show a susceptibility of MO3.13 cells to NO mediated cell death by the activation of nNOS but not of inducible NOS (iNOS). MO3.13 cells show increased susceptibility to peroxynitrite mediated cellular injury to mitochondrial proteins and decreased cell survival in the presence of LPS. Our studies suggest that the presence and activation of nNOS in oligodendrocytes can directly mediate oligodendrocyte (OC) injury and reduce cell viability.