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

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.

Shaw and Shal voltage‐gated potassium channels mediate circadian changes in Drosophila clock neuron excitability

“…Investigating the interaction of Shaw and Shal potassium with the NA sodium currents and the rescue of neuronal activity rhythms using dynamic clamp will help us to understand the possible cooperation between different ion channels in regulating rhythmic activity. In addition, this model reiterates the conservation between Drosophila and mammalian clock neuron excitability and circadian rhythms and their importance in health and disease and potential of applications to chronotherapy (Allen et al 2017;Julienne et al 2017;Zwarts et al 2017).…”

Genetically engineered animal models of Parkinson's disease: From worm to rodent

“…Although rarely systematically analysed, some non‐motor features have been observed in transgenic Drosophila (Table ). Aversive phototaxic suppression assay can be used to assess learning and memory function in transgenic Drosophila (Ali et al., ; Seugnet, Suzuki, Stidd & Shaw, ) and alterations have been reported in human WT or mutant (A53T) α‐syn overexpressing flies, as well as PINK1 and Parkin KO Drosophila (Gajula Balija, Griesinger, Herzig, Zweckstetter & Jackle, ; Julienne, Buhl, Leslie & Hodge, ). An anxiety‐like phenotype is detected in Drosophilas overexpressing the human mutant (A30P) α‐syn protein as well as in LRKK2 KO animals (De Rose, Corda, Solari, Sacchetti & Belcari, ; Zhao, Sun, Cai, Ran & Yan, ).…”

The neonicotinoid insecticide imidacloprid disrupts bumblebee foraging rhythms and sleep

“…Conventionally, an RS >2 is rhythmic, an RS of 1.5-2 is weakly rhythmic and an RS 1.5 is arrhythmic [38]. The day and night activity levels for each bee were calculated using the daynight program [62] in MATLAB. The individual bee's period length was used to split the activity data into subjective days and nights and then the activity counts for each were summed.…”