Junin virus-induced astrocytosis is impaired by iNOS inhibition.
Because Junin virus (JV) experimental encephalitis of mice and rats is characterized by mild histopathological changes that do not seem to justify per se lethality after intracerebral infection, such a murine model seems adequate to investigate the potential role of inducible nitric oxide synthase (iNOS) as a pathogenic factor. Concomitant with a predominant astrocyte reaction, increased immunoperoxidase expression of iNOS, mitochondrial superoxide dismutase (SODm) and glutathione peroxidase (GPX) was disclosed in brain of mice infected with JV strain #44. When specific inhibition of iNOS was achieved by intraperitoneal administration of amino guanidine (AG), significantly greater mortality was observed in treated animals (70% vs. 40%), together with similar infective titers ( approximately 10(7) PFU/g) but lower astrocytosis, as shown by glial fibrillary acidic (GFAP) labeling. As regards SODm and GPX immunochemical expression in neurons, no differences were found between mice with or without AG treatment. The present results suggest that the apparent protective role of nitric oxide (NO), when synthesized by iNOS, is unrelated to reduced viral replication but rather to enhanced astrocyte activation behaving as a beneficial cell response to virus-induced CNS damage.
Gómez
Ricardo M
RM
Departamento de Microbiología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Yep
Alejandra
A
Schattner
Mirta
M
Berría
María I
MI
D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic; D005911:Gliosis / Q000517:prevention & control / Q000821:virology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D018051:Junin virus / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase / Q000378:metabolism
D004791:Enzyme Inhibitors; D006146:Guanidines; D005979:Glutathione Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D013482:Superoxide Dismutase