title: Analysis of dopaminergic neuronal dysfunction in genetic and toxin-induced models of Parkinson's disease in Drosophila.
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 (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.
authors.affiliation: Institute of Zoology, University of Regensburg, Regensburg, Germany.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Navarro
authors.forename: Sabina
authors.initials: S
authors.lastname: Heßner
authors.forename: Sarat C
authors.initials: SC
authors.lastname: Yenisetti
authors.forename: Florian
authors.initials: F
authors.lastname: Bayersdorfer
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Aaron
authors.initials: A
authors.lastname: Voigt
authors.forename: Stephan
authors.initials: S
authors.lastname: Schneuwly
authors.forename: Jose A
authors.initials: JA
authors.lastname: Botella
mesh_terms: D000818:Animals; D002452:Cell Count; D059290:Dopaminergic Neurons / Q000187:drug effects*; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics; D009154:Mutation / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics; D051844:alpha-Synuclein / Q000096:biosynthesis / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
chemical_list: D029721:Drosophila Proteins; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; C111567:parkin protein; C534484:PINK1 protein, Drosophila; D000099202:PTEN-Induced Putative Kinase
keywords: animal model; drosophila; neurodegeneration; paraquat; rotenone; synuclein