Effects of MUL1 and PARKIN on the circadian clock, brain and behaviour in Drosophila Parkinson’s disease models

Bartosz Doktór,
Milena Damulewicz and
Elżbieta PyzaEmail author

BMC Neuroscience201920:24

https://doi.org/10.1186/s12868-019-0506-8

Received: 4 March 2019
Accepted: 15 May 2019
Published: 28 May 2019

Abstract

Background

Mutants 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.

Results

We 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.

Conclusions

All 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.