Restoration of the Dopamine Transporter through Cell Therapy Improves Dyskinesia in a Rat Model of Parkinson's Disease

D Tomas; D Stanic; H K Chua; K White; W C Boon; M Horne

doi:10.1371/journal.pone.0153424

Restoration of the Dopamine Transporter through Cell Therapy Improves Dyskinesia in a Rat Model of Parkinson's Disease

PLoS One. 2016 Apr 14;11(4):e0153424. doi: 10.1371/journal.pone.0153424. eCollection 2016.

Authors

D Tomas¹, D Stanic¹, H K Chua¹, K White¹, W C Boon¹, M Horne^{1

2}

Affiliations

¹ Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia, 3010.
² Department of Medicine, University of Melbourne, St Vincent's Hospital, Fitzroy, Victoria, Australia, 3065.

Abstract

The dyskinesia of Parkinson's Disease is most likely due to excess levels of dopamine in the striatum. The mechanism may be due to aberrant synthesis but also, a deficiency or absence of the Dopamine Transporter. In this study we have examined the proposition that reinstating Dopamine Transporter expression in the striatum would reduce dyskinesia. We transplanted c17.2 cells that stably expressed the Dopamine Transporter into dyskinetic rats. There was a reduction in dyskinesia in rats that received grafts expressing the Dopamine Transporter. Strategies designed to increase Dopamine Transporter in the striatum may be useful in treating the dyskinesia associated with human Parkinson's Disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Behavior, Animal / drug effects
Brain / metabolism
Brain / pathology
Cell Line
Cell- and Tissue-Based Therapy
Disease Models, Animal
Dopamine / metabolism*
Dopamine Plasma Membrane Transport Proteins / genetics
Dopamine Plasma Membrane Transport Proteins / metabolism*
Dyskinesia, Drug-Induced / etiology
Dyskinesia, Drug-Induced / metabolism
Dyskinesia, Drug-Induced / therapy
Levodopa / administration & dosage
Levodopa / pharmacology
Male
Mice
Neural Stem Cells / cytology
Neural Stem Cells / metabolism
Neural Stem Cells / transplantation*
Oxidopamine / toxicity
Parkinson Disease / metabolism
Parkinson Disease / pathology
Parkinson Disease / therapy
Rats
Rats, Wistar

Substances

Dopamine Plasma Membrane Transport Proteins
Levodopa
Oxidopamine
Dopamine

Grants and funding

MH is an NHMRC Practitioner Fellow. WCB is a Fred P. Archer Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.