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research article

The circadian clock time tunes axonal regeneration

De Virgiliis, Francesco
•
Mueller, Franziska
•
Palmisano, Ilaria
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December 5, 2023
Cell Metabolism

Nerve injuries cause permanent neurological disability due to limited axonal regeneration. Injury-dependent and-independent mechanisms have provided important insight into neuronal regeneration, however, common denominators underpinning regeneration remain elusive. A comparative analysis of transcriptomic datasets associated with neuronal regenerative ability revealed circadian rhythms as the most significantly enriched pathway. Subsequently, we demonstrated that sensory neurons possess an endogenous clock and that their regenerative ability displays diurnal oscillations in a murine model of sciatic nerve injury. Consistently, transcriptomic analysis showed a time-of-day-dependent enrichment for processes associ-ated with axonal regeneration and the circadian clock. Conditional deletion experiments demonstrated that Bmal1 is required for neuronal intrinsic circadian regeneration and target re-innervation. Lastly, lithium enhanced nerve regeneration in wild-type but not in clock-deficient mice. Together, these findings demon-strate that the molecular clock fine-tunes the regenerative ability of sensory neurons and propose com-pounds affecting clock pathways as a novel approach to nerve repair.

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Type
research article
DOI
10.1016/j.cmet.2023.10.012
Web of Science ID

WOS:001134588200001

Author(s)
De Virgiliis, Francesco
Mueller, Franziska
Palmisano, Ilaria
Chadwick, Jessica Sarah
Luengo-Gutierrez, Lucia
Giarrizzo, Angela
Yan, Yuyang
Danzi, Matt Christopher
Picon-Munoz, Carmen
Zhou, Luming
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Date Issued

2023-12-05

Publisher

Cell Press

Published in
Cell Metabolism
Volume

35

Issue

12

Start page

2153

End page
Subjects

Life Sciences & Biomedicine

•

Lithium

•

Architecture

•

Components

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPCOURTINE  
FunderGrant Number

Department of Brain Sciences, Imperial College London

Rosetrees Trust

National Institute for Health Research (NIHR) , Imperial Biomedical Research Centre

Available on Infoscience
February 20, 2024
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/204866
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