Age-related loss of axonal regeneration is reflected by the level of local translation

van Erp, Susan, van Berkel, Annemiek A., Feenstra, Eline M., Sahoo, Pabitra K., Wagstaff, Laura J., Twiss, Jeffery L., Fawcett, James W., Eva, Richard and ffrench-Constant, Charles ORCID: https://orcid.org/0000-0002-5621-3377 (2021) Age-related loss of axonal regeneration is reflected by the level of local translation. Experimental Neurology, 339. ISSN 0014-4886

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Abstract

Regeneration capacity is reduced as CNS axons mature. Using laser-mediated axotomy, proteomics and puromycin-based tagging of newly-synthesized proteins in a human embryonic stem cell-derived neuron culture system that allows isolation of axons from cell bodies, we show here that efficient regeneration in younger axons (d45 in culture) is associated with local axonal protein synthesis (local translation). Enhanced regeneration, promoted by co-culture with human glial precursor cells, is associated with increased axonal synthesis of proteins, including those constituting the translation machinery itself. Reduced regeneration, as occurs with the maturation of these axons by d65 in culture, correlates with reduced levels of axonal proteins involved in translation and an inability to respond by increased translation of regeneration promoting axonal mRNAs released from stress granules. Together, our results provide evidence that, as in development and in the PNS, local translation contributes to CNS axon regeneration.

Item Type: Article
Additional Information: Funding Information: Grants supporting this study were EMBO ALTF 1436-2015 (SvE), MS Society UK Research Grant 79 (CffC and SvE), Neurostemcellrepair FP7 (CffC), Wellcome Trust Investigator award 104783/Z/14/Z (CffC). This study was furthermore made possible by funding from National Institutes of Health to JLT ( R01-NS117821 ) and South Carolina Spinal Cord Injury Research fund to PKS ( 2019-PD-02 ).
Uncontrolled Keywords: axon regeneration,axotomy,human stem cells,in vitro live imaging,local translation,proteomics,neurology,developmental neuroscience ,/dk/atira/pure/subjectarea/asjc/2800/2808
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 20 Jul 2022 09:30
Last Modified: 02 Aug 2022 00:25
URI: https://ueaeprints.uea.ac.uk/id/eprint/86706
DOI: 10.1016/j.expneurol.2020.113594

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