Enriched conditioning expands the regenerative ability of sensory neurons after spinal cord injury via neuronal intrinsic redox signaling

• DOI: 10.1038/s41467-020-20179-z
• Publication Date: 2020-12-21T11:03:19Z
• Authors: Francesco De Virg...; Thomas H. Hutson; Ilaria Palmisano; Sarah Amachree; Jian Miao; Luming Zhou; Rositsa Todorova; Richard Thompson; Matt C. Danzi; Vance P. Lemmon; John L. Bixby; Ilka Wittig; Ajay M. Shah; Simone Di Giovanni
• Keywords: STAT3 Transcription Factor; 0301 basic medicine; Sensory Receptor Cells; Science; Neuronal Outgrowth; 610; Article; 03 medical and health sciences; Ganglia, Spinal; Animals; Phosphorylation; Promoter Regions, Genetic; Protein Kinase C; Spinal Cord Injuries; Neuronal Plasticity; Q; Axotomy; Sciatic Nerve; Axons; Nerve Regeneration; Mice, Inbred C57BL; Protein Subunits; NADPH Oxidase 2; Reactive Oxygen Species; Oxidation-Reduction; Signal Transduction

Overcoming the restricted axonal regenerative ability that limits functional repair following a central nervous system injury remains challenge. Here we report paradigm call enriched conditioning, which combines environmental enrichment (EE) followed by conditioning sciatic nerve axotomy precedes spinal cord (SCI). Enriched significantly increases of dorsal root ganglia (DRG) sensory neurons compared to EE or alone, propelling axon growth well beyond site. Mechanistically, established relies on unique neuronal intrinsic signaling axis PKC-STAT3-NADPH oxidase 2 (NOX2), enhancing redox as shown proteomics in DRG. Finally, NOX2 conditional deletion overexpression respectively blocked phenocopied conditioning-dependent regeneration after SCI leading improved recovery. These studies provide drives offering potential redox-dependent model for mechanistic and therapeutic discoveries.