Evidence for oxidative damage in a murine leukemia virus-induced neurodegeneration.
Vacuolation in cellular organelles within the central nervous system is a common manifestation of oxidative injury. We found that the spongiform vacuolation observed in PVC-211 murine leukemia virus (PVC-MuLV) neurodegeneration was associated with oxidative damage as detected by immunoreactivity for 3-nitrotyrosine and protein carbonyl groups. This oxidative injury was present in brain before or concomitant with the appearance of activated microglia, vacuolation, and gliosis that characterize PVC-MuLV neuropathology. Treatment of infected F344 rat pups with the antioxidant vitamin E transiently protected and prolonged the latency of PVC-MuLV neurodegeneration. Taken together, these findings implicate oxidative damage and lipid peroxidation in the pathogenesis of PVC-MuLV neurodegeneration. This animal model may be useful for studies of mechanisms and potential therapies for progressive neurodegeneration following a well-defined insult.
Wilt
S G
SG
Research Service, Department of Veterans Affairs Medical Center, Baltimore, Maryland 21201, USA. swilt@umaryland.edu
Dugger
N V
NV
Hitt
N D
ND
Hoffman
P M
PM
D016475:3T3 Cells; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000821:virology; D020805:Central Nervous System Viral Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D019587:Dietary Supplements; D009052:Leukemia Virus, Murine / Q000472:pathogenicity*; D051379:Mice; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D014617:Vacuoles / Q000473:pathology; D014810:Vitamin E / Q000008:administration & dosage
D015415:Biomarkers; D014810:Vitamin E