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

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  • Michaëla Majcin Dorcikova

    (University of Geneva)

  • Lou C. Duret

    (University of Geneva)

  • Emma Pottié

    (University of Geneva)

  • Emi Nagoshi

    (University of Geneva)

Abstract

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.

Suggested Citation

  • Michaëla Majcin Dorcikova & Lou C. Duret & Emma Pottié & Emi Nagoshi, 2023. "Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41540-y
    DOI: 10.1038/s41467-023-41540-y
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    References listed on IDEAS

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    1. Brigitte Grima & Elisabeth Chélot & Ruohan Xia & François Rouyer, 2004. "Morning and evening peaks of activity rely on different clock neurons of the Drosophila brain," Nature, Nature, vol. 431(7010), pages 869-873, October.
    2. Pedro Machado Almeida & Blanca Lago Solis & Luca Stickley & Alexis Feidler & Emi Nagoshi, 2021. "Neurofibromin 1 in mushroom body neurons mediates circadian wake drive through activating cAMP–PKA signaling," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    3. Chang Liu & Pierre-Yves Plaçais & Nobuhiro Yamagata & Barret D. Pfeiffer & Yoshinori Aso & Anja B. Friedrich & Igor Siwanowicz & Gerald M. Rubin & Thomas Preat & Hiromu Tanimoto, 2012. "A subset of dopamine neurons signals reward for odour memory in Drosophila," Nature, Nature, vol. 488(7412), pages 512-516, August.
    4. Federico Miozzo & Eva P. Valencia-Alarcón & Luca Stickley & Michaëla Majcin Dorcikova & Francesco Petrelli & Damla Tas & Nicolas Loncle & Irina Nikonenko & Peter Bou Dib & Emi Nagoshi, 2022. "Maintenance of mitochondrial integrity in midbrain dopaminergic neurons governed by a conserved developmental transcription factor," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
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