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

Hussain, A., Pooryasin, A., Zhang, M., Loschek, L. F., La Fortezza, M., Friedrich, A. B., et al. (2018). Inhibition of oxidative stress in cholinergic projection neurons fully rescues aging-associated olfactory circuit degeneration in Drosophila. eLife, 7: e32018. doi:10.7554/eLife.32018.

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 Creators:
Hussain, Ashiq, Author
Pooryasin, Atefeh, Author
Zhang, Mo1, Author           
Loschek, Laura F.1, Author           
La Fortezza, Marco, Author
Friedrich, Anja B., Author
Blais, Catherine-Marie, Author
Üçpunar, Habibe K.1, Author           
Yepez, Vicente A., Author
Lehmann, Martin, Author
Gompel, Nicolas, Author
Gagneur, Julien, Author
Sigrist, Stephan J., Author
Grunwald Kadow, Ilona C.1, Author           
Affiliations:
1Max Planck Research Group: Chemosensory coding / Grunwald-Kadow, MPI of Neurobiology, Max Planck Society, ou_1113556              

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Free keywords: PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; GUT MICROBIOTA; LONGEVITY; MITOCHONDRIA; SUPEROXIDE; RECEPTORS; RELEASE; SYSTEM; GROWTHLife Sciences & Biomedicine - Other Topics;
 Abstract: Loss of the sense of smell is among the first signs of natural aging and neurodegenerative diseases such as Alzheimers and Parkinsons. 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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Language(s): eng - English
 Dates: 2018-01-18
 Publication Status: Published in print
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 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000423512900001
DOI: 10.7554/eLife.32018
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Title: eLife
Source Genre: Journal
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Publ. Info: Cambridge : eLife Sciences Publications
Pages: - Volume / Issue: 7 Sequence Number: e32018 Start / End Page: - Identifier: ISSN: 2050-084X
CoNE: https://pure.mpg.de/cone/journals/resource/2050-084X