Drosophila PINK1 and parkin loss-of-function mutants display a range of non-motor Parkinson's disease phenotypes

Hannah R M Julienne, Edgar Buhl, David S Leslie, James J L Hodge*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

60 Citations (Scopus)
390 Downloads (Pure)

Abstract

Parkinson’s disease (PD) is more commonly associated with its motor symptoms and the related degeneration of dopamine (DA) neurons. However, it is becoming increasingly clear that PD patients also display a wide range of non-motor symptoms, including memory deficits and disruptions of their sleep-wake cycles. These have a large impact on their quality of life, and often precede the onset of motor symptoms, but their etiology is poorly understood. The fruit fly Drosophila has already been successfully used to model PD, and has been used extensively to study relevant non-motor behaviours in other contexts, but little attention has yet been paid to modelling non-motor symptoms of PD in this genetically tractable organism. We examined memory performance and circadian rhythms in flies with loss-of-function mutations in two PD genes: PINK1 and parkin. We found learning and memory abnormalities in both mutant genotypes, as well as a weakening of circadian rhythms that is underpinned by electrophysiological changes in clock neurons. Our study paves the way for further work that may help us understand the mechanisms underlying these neglected aspects of PD, thus identifying new targets for treatments to address these non-motor problems specifically and perhaps even to halt disease progression in its prodromal phase.
Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalNeurobiology of Disease
Volume104
Early online date21 Apr 2017
DOIs
Publication statusPublished - 1 Aug 2017

Keywords

  • Parkinson's disease
  • Non-motor symptoms
  • PINK1
  • Parkin
  • Drosophila
  • Learning
  • Memory
  • Circadian rhythms
  • Sleep
  • Electrophysiology

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