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| Status |
Public on Aug 27, 2020 |
| Title |
Identification of transcriptional alterations that distinguish sensitive from insensitive neuronal populations in a genetic model of Parkinson’s disease. |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by array
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| Summary |
Loss-of-function mutations in the parkin gene can cause early onset Parkinson’s disease, a movement disorder resulting from the selective degeneration of dopaminergic neurons in the basal ganglia. Analogously, movement deficits and loss of a subset of dopaminergic neurons are observed in Drosophila melanogaster homozygous for null mutations in parkin. Parkin is an E3 ubiquitin ligase that functions with the mitochondrial localized serine/threonine kinase PINK1 in a pathway required to maintain mitochondrial integrity. We previously established that the PINK1/Parkin pathway functions in Drosophila dopaminergic and cholinergic neurons to maintain mitochondrial membrane potential. However, the mechanisms through which the PINK/Parkin pathway selectively impacts dopaminergic neuron survival remains unclear, as do the mechanisms that lead to the selective vulnerability of dopaminergic neurons in Parkinson’s disease. Because the transcriptome of a cell determines its identity we hypothesized that knowledge of the transcriptional alterations that occur in dopaminergic neurons isolated from parkin null Drosophila would provide insight into the mystery of selective vulnerability in Parkinson's disease. Results: To test our hypothesis we measured the transcriptome of dopaminergic and cholinergic neurons isolated from isogenic heterozygous and homozygous parkin null mutants using a novel flow cytometry-based method we developed. Computational analysis and experimental confirmation demonstrate that our method allows for the successful expression analysis of defined neural subsets from the Drosophila brain. In addition, our dataset implicates iron handling and dopamine signaling as being significantly dysregulated in parkin null dopaminergic neurons. Conclusions: Our flow cytometry-based method allows for the isolation and microarray analysis of neuronal subsets from the adult Drosophila brain. Our microarray analyses implicate iron handling and dopamine metabolism as contributing factors in the etiology of parkin-associated early onset Parkinson’s disease. Here we provide a novel dataset that may serve as a foundation for subsequent functional analyses of the pathways underlying neuronal selective vulnerability in Parkinson's disease.
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| Overall design |
Three replicates of 115 dopaminergic neurons or cholinergic neurons for mutant and control parkin null animals (a total of 12 samples).
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| Contributor(s) |
Burman JL, Hariharan R |
| Citation missing |
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| Submission date |
Apr 14, 2016 |
| Last update date |
Aug 29, 2020 |
| Contact name |
James William MacDonald |
| E-mail(s) |
jmacdon@uw.edu
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| Organization name |
University of Washington
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| Department |
Environmental and Occupational Health Sciences
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| Street address |
4225 Roosevelt Way NE
|
| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98105-6099 |
| Country |
USA |
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| Platforms (1) |
| GPL1322 |
[Drosophila_2] Affymetrix Drosophila Genome 2.0 Array |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA318482 |
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