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

Autor: Hannah, Julienne, Edgar, Buhl, David S, Leslie, James J L, Hodge
Rok vydání: 2016
Předmět:
Patch-Clamp Techniques
Ubiquitin-Protein Ligases
Parkinson's disease
PINK1
PTEN-induced putative kinase 1
Non-motor symptoms
Protein Serine-Threonine Kinases
DD
Constant darkness
RBD
REM sleep behaviour disorder
PD
Parkinson's disease
Article
Membrane Potentials
SFR
Spontaneous firing rate
Animals
Genetically Modified
Memory
l-LNv
Large ventral lateral neurons
Animals
Drosophila Proteins
Learning
Circadian rhythms
Maze Learning
Parkin
Neurons
RS
Rhythmicity statistic
MCH
4-methylcyclohexanol
Learning Disabilities
DA
Dopamine
PINK1
Brain
Parkinson Disease
RMP
Resting Membrane Potential
Rin
Membrane input resistance
LD
12:12 h light-dark cycle
Circadian Rhythm
Electrophysiology
Disease Models
Animal
DAM2
Drosophila Activity Monitor
Mutation
Odorants
ZT
Zeitgeber time
Drosophila
RNA Interference
OCT
3-octanol
PI
Performance Index
Sleep
D/NI
Diurnal/nocturnal index
Locomotion
Zdroj: Neurobiology of Disease
ISSN: 1095-953X
Popis: 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.
Highlights • Drosophila PINK1 and parkin loss-of-function (LOF) mutants have memory deficits. • Drosophila PINK1 and parkin LOF mutants have weakened circadian rhythms. • Drosophila PINK1 and parkin LOF mutants have clock neuron electrophysiology defects. • Drosophila is a powerful model for studying Parkinson's disease non-motor symptoms.
Databáze: OpenAIRE
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