Wilt S G, Dugger N V, Hitt N D, Hoffman P M
Research Service, Department of Veterans Affairs Medical Center, Baltimore, Maryland 21201, USA.
J Neurosci Res. 2000 Nov 1;62(3):440-50. doi: 10.1002/1097-4547(20001101)62:3<440::AID-JNR14>3.0.CO;2-M.
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.
中枢神经系统内细胞器的空泡化是氧化损伤的常见表现。我们发现，在PVC - 211鼠白血病病毒（PVC - MuLV）神经退行性变中观察到的海绵状空泡化与氧化损伤有关，这可通过对3 - 硝基酪氨酸和蛋白质羰基的免疫反应性检测到。这种氧化损伤在脑内出现活化小胶质细胞、空泡化和胶质增生（这些是PVC - MuLV神经病理学的特征）之前或同时就已存在。用抗氧化剂维生素E治疗受感染的F344大鼠幼崽可暂时起到保护作用，并延长PVC - MuLV神经退行性变的潜伏期。综上所述，这些发现表明氧化损伤和脂质过氧化在PVC - MuLV神经退行性变的发病机制中起作用。这种动物模型可能有助于研究明确损伤后进行性神经退行性变的机制和潜在治疗方法。
