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

Neurobiology of Disease

David S. Leslie¹  Hannah Julienne²  James J.L. Hodge²  Edgar Buhl² 

[1] Department of Mathematics and Statistics, Fylde College, Lancaster University, Lancaster LA1 4YF, United Kingdom;School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, United Kingdom;

关键词: Parkinson's disease;    Non-motor symptoms;    PINK1;    Parkin;    Drosophila;    Learning;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown