Abstract
Parkinson’s disease (PD) is the most common motor neurodegenerative disorder. Olfactory dysfunction is a prevalent feature of PD. It often precedes motor symptoms by several years and is used in assisting PD diagnosis. However, the cellular and molecular bases of olfactory dysfunction in PD are not known. The fruit fly Drosophila melanogaster, expressing human alpha-synuclein protein or its mutant, A30P, captures several hallmarks of PD and has been successfully used to model PD in numerous studies. First, we report olfactory deficits in fly expressing A30P (A30P), showing deficits in two out of three olfactory modalities, tested – olfactory acuity and odor discrimination. The remaining third modality is odor identification/naming. Second, oxidative stress is an important environmental risk factor of PD. We show that oxidative stress exacerbated the two affected olfactory modalities in younger A30P flies. Third, different olfactory receptor neurons are activated differentially by different odors in flies. In a separate experiment, we show that the odor discrimination deficit in A30P flies is general and not restricted to a specific class of chemical structure. Lastly, by restricting A30P expression to dopamine, serotonin or olfactory receptor neurons, we show that A30P expression in dopamine neurons is necessary for development of both acuity and discrimination deficits, while serotonin and olfactory receptor neurons appeared not involved. Our data demonstrate olfactory deficits in a synuclein fly PD model for exploring olfactory pathology and physiology, and for monitoring PD progression and treatment.
Highlights
Parkinson’s disease (PD) is a motor degenerative disease, preferentially affecting the dopamine system
PD fly model, we used immunoblotting and showed that A30P protein was expressed in the heads of A30P flies, carrying both a pan-neural Elav-gal4 driver and an UAS-A30P transgene, but not in Control (CT) flies that carried only UAS-A30P transgenes (Figure 1A)
We found a lower percentage of A30P flies reaching the far right fifth and sixth tube, receiving a score of 4 and 5, respectively, while a higher percentage of A30P flies (59.98%) was retained in the first tube after five trials, receiving a score of zero (**P,0.01; Figure 1C, left)
Summary
Parkinson’s disease (PD) is a motor degenerative disease, preferentially affecting the dopamine system. Olfactory impairments in PD patients are prevalent, affecting 80 to 90% of both idiopathic PD patients and familial parkinsonism [4,5,6] They comprise deficits in all three functional domains: odor threshold (acuity), identification and discrimination [7,8,9]. Therapeutic intervention is best to be administrated early during disease progress, prior to significant neurodegeneration For this reason, early diagnosis and differential diagnosis of PD from other motor disorders, such as vascular parkinsonism, Methylphenyltetrahydropyridine-induced parkinsonism, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are important and can be facilitated by assessing olfactory functions [9,12,13,14]
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