title: Olfactory deficits in an alpha-synuclein fly model of Parkinson's disease.
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.
authors.affiliation: Dart Neuroscience LLC, San Diego, California, United States of America; Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America; Graduate Program in Neuroscience, SUNY Stony Brook, Stony Brook, New York, United States of America.
authors.forename: Alex Y
authors.initials: AY
authors.lastname: Chen
authors.affiliation: Dart Neuroscience LLC, San Diego, California, United States of America.
authors.forename: Shouzhen
authors.initials: S
authors.lastname: Xia
authors.affiliation: W.K. Kellogg Biological Station, Michigan State University, Hickory Corners, Michigan, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Wilburn
authors.affiliation: Dart Neuroscience LLC, San Diego, California, United States of America; Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America.
authors.forename: Tim
authors.initials: T
authors.lastname: Tully
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D004192:Discrimination, Psychological; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000473:pathology; D004331:Drosophila melanogaster; D006801:Humans; D009043:Motor Activity; D055696:Olfactory Perception; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein