Prion Cell Biology Unit, Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America.
Veterinary Biology Unit, Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America.
PLoS One. 2021 Nov 4;16(11):e0259597. doi: 10.1371/journal.pone.0259597. eCollection 2021.
Prion diseases are progressive, neurodegenerative diseases affecting humans and animals. Also known as the transmissible spongiform encephalopathies, for the hallmark spongiform change seen in the brain, these diseases manifest increased oxidative damage early in disease and changes in antioxidant enzymes in terminal brain tissue. Superoxide dismutase 2 (SOD2) is an antioxidant enzyme that is critical for life. SOD2 knock-out mice can only be kept alive for several weeks post-birth and only with antioxidant therapy. However, this results in the development of a spongiform encephalopathy. Consequently, we hypothesized that reduced levels of SOD2 may accelerate prion disease progression and play a critical role in the formation of spongiform change. Using SOD2 heterozygous knock-out and litter mate wild-type controls, we examined neuronal long-term potentiation, disease duration, pathology, and degree of spongiform change in mice infected with three strains of mouse adapted scrapie. No influence of the reduced SOD2 expression was observed in any parameter measured for any strain. We conclude that changes relating to SOD2 during prion disease are most likely secondary to the disease processes causing toxicity and do not influence the development of spongiform pathology.
朊病毒病是一种影响人类和动物的进行性神经退行性疾病。也称为传染性海绵状脑病，因为在大脑中可见到标志性的海绵状变化，这些疾病在疾病早期表现出氧化损伤增加，并且终末脑组织中的抗氧化酶发生变化。超氧化物歧化酶 2（SOD2）是一种对生命至关重要的抗氧化酶。SOD2 敲除小鼠只能在出生后存活数周，并且只能通过抗氧化治疗。然而，这会导致海绵状脑病的发展。因此，我们假设 SOD2 水平降低可能会加速朊病毒病的进展，并在海绵状变化的形成中发挥关键作用。使用 SOD2 杂合敲除和同窝野生型对照小鼠，我们检查了感染三种小鼠适应的瘙痒病的小鼠的神经元长时程增强、疾病持续时间、病理学和海绵状变化程度。在任何一种菌株的任何测量参数中，都没有观察到 SOD2 表达降低的影响。我们得出结论，朊病毒病期间与 SOD2 相关的变化很可能是疾病过程导致毒性的继发结果，并且不会影响海绵状病理学的发展。
