BACKGROUND Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by polyglutamine (CAG) expansion in the Huntingtin (HTT) gene. The CAG140 knock-in (KI) mouse model recapitulates the progression of motor symptoms emerging at 12 months of age. OBJECTIVE This study was aimed at assessing the effects of exercise, in the form of treadmill running, and examining its impact on motor behavior and markers of metabolism in the CAG140 KI mouse model of HD after motor symptoms have emerged. METHODS CAG140 KI mice at 13-15 months of age were subjected to treadmill exercise 3 days per week for 1 h per day or remained sedentary. After 12 weeks of exercise brain tissues were analyzed for enzymatic activity including mitochondria Complexes I, II/III, and IV, transglutaminase, aconitase, pyruvate dehydrogenase, and phosphofructokinase1/2. In addition, the concentration was determined for nitrate/nitrite, pyruvate carboxylase, NAD+/NADH, and glutamate as well as the ratio of mitochondria and nuclear DNA. Motor behavior was tested using the rotarod. RESULTS Exercise resulted in increased [nitrite + nitrate] levels (surmised as nitric oxide), reduced transglutaminase activity, increased aconitase activity with increased tricarboxylic acid-generated reducing equivalents and mitochondrial oxidative phosphorylation complexes activity. Mitochondrial function was strengthened by increases in glycolysis, pyruvate dehydrogenase activity, and anaplerosis component represented by pyruvate carboxylase. CONCLUSIONS These changes in mitochondrial function were associated with improved motor performance on the rotarod test. These findings suggest that exercise may have beneficial effects on motor behavior by reversing deficits in mitochondrial function in a rodent model of HD.

中文翻译：

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跑步机运动可在亨廷顿氏病的CAG140敲入小鼠模型中挽救线粒体功能和运动行为。

背景技术亨廷顿舞蹈病（HD）是由亨廷顿蛋白（HTT）基因中的聚谷氨酰胺（CAG）扩增引起的常染色体显性遗传性神经退行性疾病。CAG140敲入（KI）小鼠模型概括了12个月大时出现的运动症状的进展。目的本研究旨在评估运动的影响，以跑步机的形式运行，并检查运动症状出现后对CAG140 KI HD小鼠模型的运动行为和代谢标志物的影响。方法对13-15个月大的CAG140 KI小鼠每周进行3天的跑步机锻炼，每天1 h或久坐不动。运动12周后，分析脑组织的酶活性，包括线粒体复合物I，II / III和IV，转谷氨酰胺酶，乌头酸酶，丙酮酸脱氢酶，和磷酸果糖激酶1/2。此外，测定了硝酸盐/亚硝酸盐，丙酮酸羧化酶，NAD + / NADH和谷氨酸的浓度，以及线粒体和核DNA的比例。使用旋转脚架对运动行为进行了测试。结果运动导致[亚硝酸盐+硝酸盐]水平升高（推测为一氧化氮），转谷氨酰胺酶活性降低，乌头酸酶活性升高，三羧酸生成的还原当量升高，线粒体氧化磷酸化复合物活性升高。线粒体功能通过糖酵解，丙酮酸脱氢酶活性和丙酮酸羧化酶代表的抗动脉粥样硬化组分的增强而增强。结论线粒体功能的这些变化与轮转试验中运动能力的改善有关。