期刊
NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41467-020-20179-z
关键词
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资金
- Wings for Life
- Rosetrees Trust
- Leverhulme Trust
- MRC
- Weizmann-UK
- Department of Brain Sciences, Imperial College London
- Miami Project to Cure Paralysis
- Walter G. Ross Foundation
- National Institute for Health (NIH) [R01 HD057632]
- British Heart Foundation [CH/1999001/11735]
- Deutsche Forschungsgemeinschaft (DFG) [SFB 815/Z1]
- MRC [MR/R005311/1] Funding Source: UKRI
Pre conditioning injury or environmental enrichment have been shown to promote axon regeneration. Here the authors show that environmental enrichment, combined with preconditioning injury promotes regeneration via a redox signalling dependent mechanism. Overcoming the restricted axonal regenerative ability that limits functional repair following a central nervous system injury remains a challenge. Here we report a regenerative paradigm that we call enriched conditioning, which combines environmental enrichment (EE) followed by a conditioning sciatic nerve axotomy that precedes a spinal cord injury (SCI). Enriched conditioning significantly increases the regenerative ability of dorsal root ganglia (DRG) sensory neurons compared to EE or a conditioning injury alone, propelling axon growth well beyond the spinal injury site. Mechanistically, we established that enriched conditioning relies on the unique neuronal intrinsic signaling axis PKC-STAT3-NADPH oxidase 2 (NOX2), enhancing redox signaling as shown by redox proteomics in DRG. Finally, NOX2 conditional deletion or overexpression respectively blocked or phenocopied enriched conditioning-dependent axon regeneration after SCI leading to improved functional recovery. These studies provide a paradigm that drives the regenerative ability of sensory neurons offering a potential redox-dependent regenerative model for mechanistic and therapeutic discoveries.
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