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Analysis of dopaminergic neuronal dysfunction in genetic and toxin‐induced models of Parkinson's disease in Drosophila
Author(s) -
Navarro Juan A.,
Heßner Sabina,
Yenisetti Sarat C.,
Bayersdorfer Florian,
Zhang Li,
Voigt Aaron,
Schneuwly Stephan,
Botella Jose A.
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12818
Subject(s) - dopaminergic , biology , drosophila melanogaster , tyrosine hydroxylase , neuroscience , parkinson's disease , genetic model , phenotype , green fluorescent protein , parkin , neurodegeneration , pink1 , model organism , dopamine , microbiology and biotechnology , disease , genetics , gene , pathology , medicine
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 (α ‐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 .Analyzing three genetic and two toxin‐based Drosophila models of Parkinson's disease (PD) through green fluorescent protein reporter and α‐tyrosine hydroxylase staining, we have found the number of dopaminergic neurons to remain unchanged. Despite the lack of neuronal loss, we have detected a remarkable decrease in a reporter green‐fluorescent protein (GFP) signal in dopaminergic neurons, suggesting an abnormal neuronal status that correlates with the phenotypes associated with those PD fly models.