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Inhibition of oxidative stress in cholinergic projection neurons fully rescues aging-associated olfactory circuit degeneration in Drosophila

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...

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Autores principales: Hussain, Ashiq, Pooryasin, Atefeh, Zhang, Mo, Loschek, Laura F, La Fortezza, Marco, Friedrich, Anja B, Blais, Catherine-Marie, Üçpunar, Habibe K, Yépez, Vicente A, Lehmann, Martin, Gompel, Nicolas, Gagneur, Julien, Sigrist, Stephan J, Grunwald Kadow, Ilona C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790380/
https://www.ncbi.nlm.nih.gov/pubmed/29345616
http://dx.doi.org/10.7554/eLife.32018
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author Hussain, Ashiq
Pooryasin, Atefeh
Zhang, Mo
Loschek, Laura F
La Fortezza, Marco
Friedrich, Anja B
Blais, Catherine-Marie
Üçpunar, Habibe K
Yépez, Vicente A
Lehmann, Martin
Gompel, Nicolas
Gagneur, Julien
Sigrist, Stephan J
Grunwald Kadow, Ilona C
author_facet Hussain, Ashiq
Pooryasin, Atefeh
Zhang, Mo
Loschek, Laura F
La Fortezza, Marco
Friedrich, Anja B
Blais, Catherine-Marie
Üçpunar, Habibe K
Yépez, Vicente A
Lehmann, Martin
Gompel, Nicolas
Gagneur, Julien
Sigrist, Stephan J
Grunwald Kadow, Ilona C
author_sort Hussain, Ashiq
collection PubMed
description 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 suggest 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.
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spelling pubmed-57903802018-01-31 Inhibition of oxidative stress in cholinergic projection neurons fully rescues aging-associated olfactory circuit degeneration in Drosophila Hussain, Ashiq Pooryasin, Atefeh Zhang, Mo Loschek, Laura F La Fortezza, Marco Friedrich, Anja B Blais, Catherine-Marie Üçpunar, Habibe K Yépez, Vicente A Lehmann, Martin Gompel, Nicolas Gagneur, Julien Sigrist, Stephan J Grunwald Kadow, Ilona C eLife Neuroscience 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 suggest 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. eLife Sciences Publications, Ltd 2018-01-18 /pmc/articles/PMC5790380/ /pubmed/29345616 http://dx.doi.org/10.7554/eLife.32018 Text en © 2018, Hussain et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Hussain, Ashiq
Pooryasin, Atefeh
Zhang, Mo
Loschek, Laura F
La Fortezza, Marco
Friedrich, Anja B
Blais, Catherine-Marie
Üçpunar, Habibe K
Yépez, Vicente A
Lehmann, Martin
Gompel, Nicolas
Gagneur, Julien
Sigrist, Stephan J
Grunwald Kadow, Ilona C
Inhibition of oxidative stress in cholinergic projection neurons fully rescues aging-associated olfactory circuit degeneration in Drosophila
title Inhibition of oxidative stress in cholinergic projection neurons fully rescues aging-associated olfactory circuit degeneration in Drosophila
title_full Inhibition of oxidative stress in cholinergic projection neurons fully rescues aging-associated olfactory circuit degeneration in Drosophila
title_fullStr Inhibition of oxidative stress in cholinergic projection neurons fully rescues aging-associated olfactory circuit degeneration in Drosophila
title_full_unstemmed Inhibition of oxidative stress in cholinergic projection neurons fully rescues aging-associated olfactory circuit degeneration in Drosophila
title_short Inhibition of oxidative stress in cholinergic projection neurons fully rescues aging-associated olfactory circuit degeneration in Drosophila
title_sort inhibition of oxidative stress in cholinergic projection neurons fully rescues aging-associated olfactory circuit degeneration in drosophila
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790380/
https://www.ncbi.nlm.nih.gov/pubmed/29345616
http://dx.doi.org/10.7554/eLife.32018
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