PT  - JOURNAL ARTICLE
AU  - Weili Tian
AU  - Amir Asgharsharghi
AU  - Gema Valera
AU  - Tim Czopka
AU  - Melanie Haehnel-Taguchi
AU  - Hernán López-Schier
TI  - Systemic loss of Sarm1 is glioprotective after neurotrauma
AID  - 10.1101/493163
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 493163
4099  - http://biorxiv.org/content/early/2018/12/11/493163.short
4100  - http://biorxiv.org/content/early/2018/12/11/493163.full
AB  - Protecting the nervous system from chronic effects of physical and chemical stress is a pressing clinical challenge, which has sparked intense efforts to identify molecular inhibitors of axon destruction. Yet, one caveat of such strategy is the extent of unintended deleterious effects of blocking axon degeneration systemically. Here we use genetics and pharmacology in zebrafish to show that elimination of the obligate pro-degenerative protein Sarm1 is compatible with neural homeostasis and function, and is glioprotective. Severed axons lacking Sarm1 subsist independently of Schwann-cell support. Regenerating axons in Sarm1 mutants do not reseal with non-degradable axon segments and regain connectivity with peripheral synaptic targets to enable sensorimotor recovery, suggesting that neural-circuit repair is not contingent upon expeditious clearance of damaged axons. Unexpectedly, we found that Sarm1 deficiency increases Schwann-cell resistance to toxicity by diverse chemotherapeutic agents after nerve injury. Our findings anticipate that pharmacological interventions targeting Sarm1 are promising strategies to reduce chronic consequences of neurotrauma.