Olfactory deficits in an alpha-synuclein fly model of Parkinson's disease

Chen, A. Y., Xia, S., Wilburn, P., Tully, T. (May 2014) Olfactory deficits in an alpha-synuclein fly model of Parkinson's disease. PLoS ONE, 9 (5). e97758. ISSN 1932-6203 (Electronic)1932-6203 (Linking)

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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.

Item Type: Paper
Subjects: organism description > animal > insect > Drosophila
diseases & disorders > nervous system diseases and disorders > Parkinson's disease
organism description > model organism
organism description > animal behavior > olfactory
CSHL Authors:
Communities: CSHL labs > Tully lab
Depositing User: Matt Covey
Date: 30 May 2014
Date Deposited: 09 Jun 2014 19:59
Last Modified: 11 Jul 2014 16:50
PMCID: PMC4039441
Related URLs:
URI: https://repository.cshl.edu/id/eprint/30293

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