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Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila

Sleep and circadian rhythm disruptions are frequent comorbidities of Parkinson’s disease (PD), a disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, the causal role of circadian clocks in the degenerative process remains uncertain. We demonst...

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Autores principales: Majcin Dorcikova, Michaëla, Duret, Lou C., Pottié, Emma, Nagoshi, Emi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516932/
https://www.ncbi.nlm.nih.gov/pubmed/37737209
http://dx.doi.org/10.1038/s41467-023-41540-y
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author Majcin Dorcikova, Michaëla
Duret, Lou C.
Pottié, Emma
Nagoshi, Emi
author_facet Majcin Dorcikova, Michaëla
Duret, Lou C.
Pottié, Emma
Nagoshi, Emi
author_sort Majcin Dorcikova, Michaëla
collection PubMed
description Sleep and circadian rhythm disruptions are frequent comorbidities of Parkinson’s disease (PD), a disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, the causal role of circadian clocks in the degenerative process remains uncertain. We demonstrated here that circadian clocks regulate the rhythmicity and magnitude of the vulnerability of DA neurons to oxidative stress in male Drosophila. Circadian pacemaker neurons are presynaptic to a subset of DA neurons and rhythmically modulate their susceptibility to degeneration. The arrhythmic period (per) gene null mutation exacerbates the age-dependent loss of DA neurons and, in combination with brief oxidative stress, causes premature animal death. These findings suggest that circadian clock disruption promotes dopaminergic neurodegeneration.
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spelling pubmed-105169322023-09-24 Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila Majcin Dorcikova, Michaëla Duret, Lou C. Pottié, Emma Nagoshi, Emi Nat Commun Article Sleep and circadian rhythm disruptions are frequent comorbidities of Parkinson’s disease (PD), a disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, the causal role of circadian clocks in the degenerative process remains uncertain. We demonstrated here that circadian clocks regulate the rhythmicity and magnitude of the vulnerability of DA neurons to oxidative stress in male Drosophila. Circadian pacemaker neurons are presynaptic to a subset of DA neurons and rhythmically modulate their susceptibility to degeneration. The arrhythmic period (per) gene null mutation exacerbates the age-dependent loss of DA neurons and, in combination with brief oxidative stress, causes premature animal death. These findings suggest that circadian clock disruption promotes dopaminergic neurodegeneration. Nature Publishing Group UK 2023-09-22 /pmc/articles/PMC10516932/ /pubmed/37737209 http://dx.doi.org/10.1038/s41467-023-41540-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Majcin Dorcikova, Michaëla
Duret, Lou C.
Pottié, Emma
Nagoshi, Emi
Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila
title Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila
title_full Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila
title_fullStr Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila
title_full_unstemmed Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila
title_short Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila
title_sort circadian clock disruption promotes the degeneration of dopaminergic neurons in male drosophila
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516932/
https://www.ncbi.nlm.nih.gov/pubmed/37737209
http://dx.doi.org/10.1038/s41467-023-41540-y
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