Inhibition of oxidative stress in cholinergic projection neurons fully rescues aging associated olfactory circuit degeneration in Drosophila
- Technical University of Munich, Germany
- Free University of Berlin, Germany
- Max-Planck Institute of Neurobiology, Germany
- Ludwig-Maximilians-Universität München, Germany
- Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Germany
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Abstract
Loss of the sense of smell is among the first signs of natural aging and neurodegenerative diseases such as Alzheimer's and Parkinson's. Cellular and molecular mechanisms promoting this smell loss are not understood. Here, we show that Drosophila melanogaster also loses olfaction before vision with age. Within the olfactory circuit, cholinergic projection neurons show a reduced odor response accompanied by a defect in axonal integrity and reduction in synaptic marker proteins. Using behavioral functional screening, we pinpoint that expression of the mitochondrial reactive oxygen scavenger SOD2 in cholinergic projection neurons is necessary and sufficient to prevent smell degeneration in aging flies. Together, our data show that oxidative stress induced axonal degeneration in a single class of neurons drives the functional decline of an entire neural network and the behavior it controls. Given the important role of the cholinergic system in neurodegeneration, the fly olfactory system could be a useful model for the identification of drug targets.
Article and author information
Author details
Julien Gagneur
Ilona C Grunwald Kadow
Funding
H2020 European Research Council (FlyContext)
- Ilona C Grunwald Kadow
European Molecular Biology Organization (EMBO Young Investigator Small Grant)
- Ilona C Grunwald Kadow
Max-Planck-Gesellschaft (Open-access funding)
- Ilona C Grunwald Kadow
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Patrik Verstreken, Reviewing Editor, VIB-KU Leuven, Belgium
Publication history
- Received: September 14, 2017
- Accepted: January 16, 2018
- Accepted Manuscript published: January 18, 2018 (version 1)
- Version of Record published: January 30, 2018 (version 2)
Copyright
© 2018, Hussain et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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