Abstract
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.
Highlights
Mitochondria are important organelles in the metabolism of all cells, in neurons because of their high energy demand [1]
We examined whether mutations of mul1 and park genes affect the molecular mechanism of the circadian clock and clock neurons, which may lead to changes in behavioural circadian rhythms and sleep disturbance
The effect of mul1 and park mutations on the circadian clock Examination of clock gene expression showed that mul1 and park mutations disrupted their normal expression during the day
Summary
Mitochondria are important organelles in the metabolism of all cells, in neurons because of their high energy demand [1]. Several neurodegenerative diseases in which changes in mitochondrial structure and function lead to cell death [2] One of these diseases is Parkinson’s disease (PD), which can be caused by exposure to neurotoxins and/or by several gene mutations. These mutations include mutations in genes encoding PINK1, a mitochondrial kinase, and PARKIN, an E3 ubiquitin ligase, which leads to the autosomal recessive form of PD [3, 4] These proteins regulate the function and morphology of mitochondria and Doktór et al BMC Neurosci (2019) 20:24 and excessive daytime sleepiness (EDS) or insomnia [10]. Results: We found that the ROS level was higher, while the anti-oxidant enzyme SOD1 level was lower in mul1A6 and park mutants than in the white mutant used as a control Mutations of both ligases affected circadian rhythms and the clock. The lack of both ligases led to decreased longevity and climbing ability of the flies
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