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Tian, W. ; Czopka, T.* ; López-Schier, H.

Systemic loss of Sarm1 protects Schwann cells from chemotoxicity by delaying axon degeneration.

Comm. Biol. 3:49 (2020)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
Protecting the nervous system from chronic effects of physical and chemical stress is a pressing clinical challenge. The obligate pro-degenerative protein Sarm1 is essential for Wallerian axon degeneration. Thus, blocking Sarm1 function is emerging as a promising neuroprotective strategy with therapeutic relevance. Yet, the conditions that will most benefit from inhibiting Sarm1 remain undefined. Here we combine genome engineering, pharmacology and high-resolution intravital videmicroscopy in zebrafish to show that genetic elimination of Sarm1 increases Schwann-cell resistance to toxicity by diverse chemotherapeutic agents after axonal injury. Synthetic degradation of Sarm1-deficient axons reversed this effect, suggesting that glioprotection is a non-autonomous effect of delayed axon degeneration. Moreover, loss of Sarm1 does not affect macrophage recruitment to nerve-wound microenvironment, injury resolution, or neural-circuit repair. These findings anticipate that interventions aimed at inhibiting Sarm1 can counter heightened glial vulnerability to chemical stressors and may be an effective strategy to reduce chronic consequences of neurotrauma.Tian et al. showed that systemic elimination of Sarm1 in zebrafish increases Schwann-cell resistance to chemotherapeutics and protects axons from Wallerian degeneration. They use genetics, pharmacology, and high resolution intravital videomicroscopy to study Sarm1 in vivo.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Traumatic Brain-injury; Wallerian Degeneration; Nervous-system; Mitochondrial Transport; Lateral-line; Optic-nerve; Regeneration; Activation; Neurotoxicity; Mechanisms
ISSN (print) / ISBN 2399-3642
e-ISSN 2399-3642
Quellenangaben Volume: 3, Issue: 1, Pages: , Article Number: 49 Supplement: ,
Publisher Springer
Publishing Place London
Reviewing status Peer reviewed