Analysis of dopaminergic neuronal dysfunction in genetic and toxin-induced models of Parkinson's disease in Drosophila

Navarro, Juan A. and Hessner, Sabina and Yenisetti, Sarat C. and Bayersdorfer, Florian and Zhang, Li and Voigt, Aaron and Schneuwly, Stephan and Botella, Jose A. (2014) Analysis of dopaminergic neuronal dysfunction in genetic and toxin-induced models of Parkinson's disease in Drosophila. JOURNAL OF NEUROCHEMISTRY, 131 (3). pp. 369-382. ISSN 0022-3042, 1471-4159

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Abstract

Drosophila melanogaster has contributed significantly to the understanding of disease mechanisms in Parkinson's disease (PD) as it is one of the very few PD model organisms that allow the study of age-dependent behavioral defects, physiology and histology, and genetic interactions among different PD-related genes. However, there have been contradictory results from a number of recent reports regarding the loss of dopaminergic neurons in different PD fly models. In an attempt to re-evaluate and clarify this issue, we have examined three different genetic (-synuclein, Pink1, parkin) and two toxin-based (rotenone and paraquat) models of the disease for neuronal cell loss. Our results showed no dopaminergic neuronal loss in all models tested. Despite this surprising result, we found additional phenotypes showing the dysfunctional status of the dopaminergic neurons in most of the models analyzed. A common feature found in most models is a quantifiable decrease in the fluorescence of a green-fluorescent protein reporter gene in dopaminergic neurons that correlates well with other phenotypes found for these models and can be reliably used as a hallmark of the neurodegenerative process when modeling diseases affecting the dopaminergic system in Drosophila.

Item Type: Article
Uncontrolled Keywords: ALPHA-SYNUCLEIN; TYROSINE-HYDROXYLASE; MUTANTS; NEURODEGENERATION; NEUROTOXICITY; INACTIVATION; DEGENERATION; SUPPRESSION; PATHWAY; PINK1; animal model; drosophila; neurodegeneration; paraquat; rotenone; synuclein
Subjects: 500 Science > 590 Zoological sciences
Divisions: Biology, Preclinical Medicine > Institut für Zoologie > Entwicklungsbiologie (Prof. Dr. Stephan Schneuwly)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 08 Aug 2019 11:02
Last Modified: 08 Aug 2019 11:02
URI: https://pred.uni-regensburg.de/id/eprint/9305

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