BackgroundMutants which carry mutations in genes encoding mitochondrial ligases MUL1 and PARKIN are convenient Drosophila models of Parkinson’s disease (PD). In several studies it has been shown that in Parkinson’s disease sleep disturbance occurs, which may be the result of a disturbed circadian clock.ResultsWe found that the ROS level was higher, while the anti-oxidant enzyme SOD1 level was lower in mul1A6 and park1 mutants than in the white mutant used as a control. Moreover, mutations of both ligases affected circadian rhythms and the clock. The expression of clock genes per, tim and clock and the level of PER protein were changed in the mutants. Moreover, expression of ATG5, an autophagy protein also involved in circadian rhythm regulation, was decreased in the brain and in PDF-immunoreactive large ventral lateral clock neurons. The observed changes in the molecular clock resulted in a longer period of locomotor activity rhythm, increased total activity and shorter sleep at night. Finally, the lack of both ligases led to decreased longevity and climbing ability of the flies.ConclusionsAll of the changes observed in the brains of these Drosophila models of PD, in which mitochondrial ligases MUL1 and PARKIN do not function, may explain the mechanisms of some neurological and behavioural symptoms of PD.

中文翻译：

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MUL1 和 PARKIN 对果蝇帕金森病模型中生物钟、大脑和行为的影响

背景在编码线粒体连接酶 MUL1 和 PARKIN 的基因中携带突变的突变体是方便的帕金森病 (PD) 果蝇模型。多项研究表明，帕金森病患者会出现睡眠障碍，这可能是生物钟紊乱的结果。 结果我们发现 mul1A6 和 park1 突变体中 ROS 水平较高，而抗氧化酶 SOD1 水平较低比用作对照的白色突变体。此外，两种连接酶的突变都会影响昼夜节律和生物钟。突变体中时钟基因 per、tim 和clock 的表达以及PER 蛋白的水平发生了变化。此外，ATG5（一种也参与昼夜节律调节的自噬蛋白）在大脑和 PDF 免疫反应性大腹侧外侧时钟神经元中的表达降低。观察到的分子钟变化导致运动活动节律延长、总活动增加和夜间睡眠缩短。最后，缺乏这两种连接酶导致果蝇寿命和攀爬能力下降。结论在这些果蝇模型的 PD 大脑中观察到的所有变化，其中线粒体连接酶 MUL1 和 PARKIN 不起作用，可以解释一些机制PD 的神经和行为症状。