Aguiar Aderbal Silva, Duzzioni Marcelo, Remor Aline Pertile, Tristão Fabrine Sales Massafera, Matheus Filipe C, Raisman-Vozari Rita, Latini Alexandra, Prediger Rui Daniel
Laboratório Experimental de Doenças Neurodegenerativas (LEXDON), Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88049-900, Florianópolis, Brazil.
Laboratório de Bioenergética e Estresse Oxidativo (LABOX), Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88049-900, Florianópolis, Brazil.
Neurochem Res. 2016 Feb;41(1-2):64-72. doi: 10.1007/s11064-015-1709-8. Epub 2015 Sep 1.
Exercise improves the motor symptoms of patients with Parkinson disease in a palliative manner. Existing evidence demonstrates that exercise induces neuroprotection based on the neurotrophic properties. We investigated the effect of exercise on mitochondrial physiology and oxidative stress in an animal model of hemiparkinsonism.
C57BL/6 mice completed a 6-week exercise program on a treadmill. We injected 6-hydroxydopamine (6-OHDA; 4 μg/2 μl) into the midstriatum. The animals progressively developed bradykinesia and R(-)-apomorphine-induced rotations that were attenuated by exercise. Transcriptional activation of protective genes is mediated by the antioxidant response element (ARE). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) binds to ARE. We investigated the Nrf2-ARE pathway in the striatum of animals.
Exercise protected 6-OHDA-induced loss of tyrosine hydroxylase immunolabeling and activated the Nrf2-ARE pathway in the nigrostriatal pathway. Exercise stimulated mitochondrial biogenesis in the striatum of animals that was more resistant to oxidant 6-OHDA and nitric oxide donor (±)-S-nitroso-N-acetylpenicillamine.
In mice, exercise activated Nrf2-ARE signaling in the nigrostriatal pathway that was protective against the development of hemiparkinsonism.
运动以姑息方式改善帕金森病患者的运动症状。现有证据表明，运动基于神经营养特性诱导神经保护作用。我们在半侧帕金森病动物模型中研究了运动对线粒体生理学和氧化应激的影响。
C57BL/6小鼠在跑步机上完成了为期6周的运动计划。我们将6-羟基多巴胺（6-OHDA；4μg/2μl）注射到纹状体中部。动物逐渐出现运动迟缓以及R(-)-阿扑吗啡诱导的旋转，而运动可使其减轻。保护性基因的转录激活由抗氧化反应元件（ARE）介导。核因子（红系衍生2）样2（Nrf2）与ARE结合。我们研究了动物纹状体中的Nrf2-ARE通路。
运动保护了6-OHDA诱导的酪氨酸羟化酶免疫标记缺失，并激活了黑质纹状体通路中的Nrf2-ARE通路。运动刺激了动物纹状体中的线粒体生物合成，这些动物对氧化剂6-OHDA和一氧化氮供体（±）-S-亚硝基-N-乙酰青霉胺更具抗性。
在小鼠中，运动激活了黑质纹状体通路中的Nrf2-ARE信号，对半侧帕金森病的发展具有保护作用。
