Hata Yukiko, Ma Ning, Yoneda Misao, Morimoto Satoru, Okano Hideyuki, Murayama Shigeo, Kawanishi Shosuke, Kuzuhara Shigeki, Kokubo Yasumasa
Department of Neurology, Graduate School of Medicine, Mie University, Mie, Japan.
Division of Health Science, Graduate School of Health Science, Suzuka University of Medical Science, Mie, Japan.
Front Neurosci. 2018 Jan 22;11:751. doi: 10.3389/fnins.2017.00751. eCollection 2017.
The Kii Peninsula of Japan is known to be a high incidence area of amyotrophic lateral sclerosis/parkinsonism-dementia complex (Kii ALS/PDC) with tauopathy. Nitrative stress and oxidative stress on ALS/PDC and their relationship to tau pathology were clarified. Seven patients with Kii ALS/PDC (3 males and 4 females, average age 70.7 years, 3 with ALS, 2 with ALS with dementia, and 2 with PDC) were analyzed in this study. Five patients with Alzheimer's disease and five normal aged subjects were used as controls. Immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded temporal lobe sections (the hippocampal area including hippocampus, prosubiculum, subiculum, presubiculum, and parahippocampal gyri) using antibodies to detect phosphorylated tau (anti-AT-8), nitrated guanine (anti-8-NG), anti-iNOS, anti-NFκB, and oxidized guanine (anti-8-OHdG) antibodies. Most hippocampal neurons of Kii ALS/PDC patients were stained with anti-8-NG, anti-iNOS, anti-NFκB, and anti-8-OHdG antibodies and some AT-8 positive neurons were co-stained with anti-8-NG antibody. The numbers of 8-NG positive neurons and 8-OHdG positive neurons were greater than AT-8 positive neurons and the number of 8-NG positive neurons was larger in patients with Kii ALS/PDC than in controls. Nitrative and oxidative stress may take priority over tau accumulation and lead to the neurodegeneration in Kii ALS/PDC.
日本的纪伊半岛是肌萎缩侧索硬化症/帕金森病痴呆综合征（纪伊ALS/PDC）伴tau蛋白病的高发地区。阐明了纪伊ALS/PDC中的硝化应激和氧化应激及其与tau蛋白病理学的关系。本研究分析了7例纪伊ALS/PDC患者（3例男性和4例女性，平均年龄70.7岁，3例为ALS，2例为伴痴呆的ALS，2例为PDC）。5例阿尔茨海默病患者和5例正常老年受试者作为对照。使用检测磷酸化tau蛋白（抗AT-8）、硝化鸟嘌呤（抗8-NG）、抗诱导型一氧化氮合酶、抗核因子κB和氧化鸟嘌呤（抗8-OHdG）抗体的抗体，对福尔马林固定、石蜡包埋的颞叶切片（包括海马体、前下托、下托、前下托和海马旁回的海马区）进行免疫组织化学分析。纪伊ALS/PDC患者的大多数海马神经元用抗8-NG、抗诱导型一氧化氮合酶、抗核因子κB和抗8-OHdG抗体染色，一些AT-8阳性神经元与抗8-NG抗体共染色。纪伊ALS/PDC患者中8-NG阳性神经元和8-OHdG阳性神经元的数量多于AT-8阳性神经元，且纪伊ALS/PDC患者中8-NG阳性神经元的数量多于对照组。硝化应激和氧化应激可能优先于tau蛋白积累，并导致纪伊ALS/PDC中的神经退行性变。
