EFFECT OF NEUROTROPIC VIRUS-INFECTION ON NEURONAL AND INDUCIBLE NITRIC-OXIDE SYNTHASE ACTIVITY IN RAT-BRAIN

To elucidate the potential role of inducible nitric oxide synthase (iN OS) and neuronal constitutive nitric oxide synthase (cNOS) in the path ogenesis of virus-induced encephalopathy, the activities of both NOS i soforms were determined in the brains of rats infected with Borna dise ase virus (BDV) or rabies virus. iNOS activity strongly increased, whe reas neuronal cNOS activity significantly decreased in a time-dependen t manner after either BDV or rabies virus infection. Choline acetyltra nsferase activity in the brain remained unchanged during both virus in fections, suggesting that the decrease in cNOS activity does not refle ct a generalized neuronal loss. Immunohistochemistry and Northern blot analyses indicate that the decrease in neuronal cNOS activity is due to a decrease in cNOS protein and mRNA synthesis. These results sugges t that both an excessive generation of NO by activated macrophages or microglia, as well as a decrease of NO production in neurons may contr ibute to the neuropathogenesis of neurotropic virus infections.