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

NEUROBIOLOGY OF DISEASE

卷:104

Article

Julienne, Hannah¹  Buhl, Edgar¹  Leslie, David S.²  Hodge, James J. L.¹ 

[1] Univ Bristol, Sch Physiol Pharmacol & Neurosci, Biomed Sci Bldg, Bristol BS8 1TD, Avon, England

[2] Univ Lancaster, Fylde Coll, Dept Math & Stat, Lancaster LA1 4YF, England

关键词: Parkinson's disease;    Non-motor symptoms;    PINK1;    Parkin;    Drosophila;    Learning;    Memory;    Circadian rhythms;    Sleep;    Electrophysiology;   

DOI  :  10.1016/j.nbd.2017.04.014

来源: Elsevier

【 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. Crown Copyright (C) 2017 Published by Elsevier Inc.

【 授权许可】

Free