title: Brain-Specific Superoxide Dismutase 2 Deficiency Causes Perinatal Death with Spongiform Encephalopathy in Mice.
abstract: 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.
authors: Department of Advanced Aging Medicine, Chiba University Graduate School of Medicine, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors: Naotaka
authors: N
authors: Izuo
authors: Department of Orthopedics, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Hidetoshi
authors: H
authors: Nojiri
authors: Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan.
authors: Satoshi
authors: S
authors: Uchiyama
authors: Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan.
authors: Yoshihiro
authors: Y
authors: Noda
authors: Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan.
authors: Satoru
authors: S
authors: Kawakami
authors: Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors: Shuji
authors: S
authors: Kojima
authors: Department of Medical Engineering and Technology, Kitasato University School of Allied of Health Science, Kitasato, Sagamihara, Kanagawa 252-0373, Japan ; Redox Biology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan.
authors: Toru
authors: T
authors: Sasaki
authors: Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan ; Department of Ageing Control Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Takuji
authors: T
authors: Shirasawa
authors: Department of Advanced Aging Medicine, Chiba University Graduate School of Medicine, Inohana, Chuo-ku, Chiba 260-8670, Japan ; Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan.
authors: Takahiko
authors: T
authors: Shimizu
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D066087:Perinatal Death; D013482:Superoxide Dismutase / Q000172:deficiency*; D000099156:Superoxide Dismutase 2
chemical_list: D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2