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  • the Korean Society for Brain and Neural Sciences

Article

Original Article

Exp Neurobiol 2020; 29(4): 273-284

Published online August 31, 2020

https://doi.org/10.5607/en20028

© The Korean Society for Brain and Neural Sciences

L-DOPA-Induced Dyskinesia in a Genetic Drosophila Model of Parkinson’s Disease

Joshua A. Blosser, Eric Podolsky and Daewoo Lee*

Neuroscience Program, Department of Biological Sciences, Ohio University, Athens, OH 45701, USA

Correspondence to: *To whom correspondence should be addressed.
TEL: 1-740-597-1926, FAX: 1-740-593-0300
e-mail: Leed1@ohio.edu

Received: July 11, 2020; Revised: August 27, 2020; Accepted: August 31, 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License
(http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and
reproduction in any medium, provided the original work is properly cited.

Motor symptoms in Parkinson’s disease (PD) are directly related to the reduction of a neurotransmitter dopamine. Therefore, its precursor L-DOPA became the gold standard for PD treatment. However, chronic use of L-DOPA causes uncontrollable, involuntary movements, called L-DOPA-induced dyskinesia (LID) in the majority of PD patients. LID is complicated and very difficult to manage. Current rodent and non-human primate models have been developed to study LID mainly using neurotoxins. Therefore, it is necessary to develop a LID animal model with defects in genetic factors causing PD in order to study the relation between LID and PD genes such as α-synuclein. In this study, we first showed that a low concentration of L-DOPA (100 μM) rescues locomotion defects (i.e., speed, angular velocity, pause time) in Drosophila larvae expressing human mutant α-synuclein (A53T). This A53T larval model of PD was used to further examine dyskinetic behaviors. High concentrations of L-DOPA (5 or 10 mM) causes hyperactivity such as body bending behavior (BBB) in A53T larva, which resembles axial dyskinesia in rodents. Using ImageJ plugins and other third party software, dyskinetic BBB has been accurately and efficiently quantified. Further, we showed that a dopamine agonist pramipexole (PRX) partially rescues BBB caused by high L-DOPA. Our Drosophila genetic LID model will provide an important experimental platform to examine molecular and cellular mechanisms underlying LID, to study the role of PD causing genes in the development of LID, and to identify potential targets to slow/reverse LID pathology.

Graphical Abstract


Keywords: Alpha-Synuclein, Parkinson’s disease, L-DOPA, Dyskinesia, Drosophila melanogaster