| RRC ID |
76499
|
| 著者 |
Tian W, Czopka T, López-Schier H.
|
| タイトル |
Systemic loss of Sarm1 protects Schwann cells from chemotoxicity by delaying axon degeneration.
|
| ジャーナル |
Commun Biol
|
| Abstract |
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.
|
| 巻・号 |
3(1)
|
| ページ |
49
|
| 公開日 |
2020-1-30
|
| DOI |
10.1038/s42003-020-0776-9
|
| PII |
10.1038/s42003-020-0776-9
|
| PMID |
32001778
|
| PMC |
PMC6992705
|
| MeSH |
Animals
Animals, Genetically Modified
Antineoplastic Agents / adverse effects*
Armadillo Domain Proteins / deficiency*
Armadillo Domain Proteins / genetics
Axons / metabolism*
Axons / pathology
Fluorescent Antibody Technique
Genetic Loci
Mutagenesis
Phenotype
Schwann Cells / drug effects*
Schwann Cells / metabolism*
Wallerian Degeneration / genetics*
Zebrafish
|
| IF |
4.165
|
| リソース情報 |
| ゼブラフィッシュ |
HGn39D, SAGFF(LF)202A, UAS:GFP, UAS:GCaMP7a |
