Brain-Specific Superoxide Dismutase 2 Deficiency Causes Perinatal Death with Spongiform Encephalopathy in Mice.
Brain-Specific Superoxide Dismutase 2 Deficiency Causes Perinatal Death with Spongiform Encephalopathy in Mice.
复制标题
DOI：
10.1155/2015/238914
复制
发表时间：
2015
影响因子：
--
通讯作者：
Shimizu T
中科院分区：
文献类型：
--
作者：
Izuo N;Nojiri H;Uchiyama S;Noda Y;Kawakami S;Kojima S;Sasaki T;Shirasawa T;Shimizu T
氧化应激被认为在很大程度上有助于各种疾病的发病机制，包括神经变性。线粒体能量产生受损和线粒体氧化损伤增加被认为是导致神经变性的早期病理事件。锰超氧化物歧化酶（Mn-SOD，SOD 2）是一种线粒体抗氧化酶，可将有毒的超氧化物转化为过氧化氢。为了研究线粒体氧化应激在中枢神经系统中的病理作用，我们使用nestin-Cre-loxp系统产生了脑特异性SOD 2缺陷小鼠（B-Sod 2-/-）。B-Sod 2 −/−显示围产期死亡，沿着严重的生长迟缓。有趣的是，这些小鼠在运动皮层、海马和脑干中表现出海绵状神经变性，伴有神经胶质增生。此外，根据酶组织化学，突变小鼠脑中线粒体复合体II活性显著降低，但复合体I或IV活性未降低。此外，脑脂质过氧化作用显着增加B-Sod 2 −/−，没有任何补偿性的其他抗氧化酶，如过氧化氢酶或谷胱甘肽过氧化物酶的活动的变化。这些结果表明，SOD 2保护神经系统免受围产期的氧化应激，并且对小鼠的婴儿存活和中枢神经功能至关重要。
Oxidative stress is believed to greatly contribute to the pathogenesis of various diseases, including neurodegeneration. Impairment of mitochondrial energy production and increased mitochondrial oxidative damage are considered early pathological events that lead to neurodegeneration. Manganese superoxide dismutase (Mn-SOD, SOD2) is a mitochondrial antioxidant enzyme that converts toxic superoxide to hydrogen peroxide. To investigate the pathological role of mitochondrial oxidative stress in the central nervous system, we generated brain-specific SOD2-deficient mice (B-Sod2 −/−) using nestin-Cre-loxp system. B-Sod2 −/− showed perinatal death, along with severe growth retardation. Interestingly, these mice exhibited spongiform neurodegeneration in motor cortex, hippocampus, and brainstem, accompanied by gliosis. In addition, the mutant mice had markedly decreased mitochondrial complex II activity, but not complex I or IV, in the brain based on enzyme histochemistry. Furthermore, brain lipid peroxidation was significantly increased in the B-Sod2 −/−, without any compensatory alterations of the activities of other antioxidative enzymes, such as catalase or glutathione peroxidase. These results suggest that SOD2 protects the neural system from oxidative stress in the perinatal stage and is essential for infant survival and central neural function in mice.