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

Abstract：

: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.

journal_name

Nat Commun

journal_title

Nature communications

authors

De Virgiliis F,Hutson TH,Palmisano I,Amachree S,Miao J,Zhou L,Todorova R,Thompson R,Danzi MC,Lemmon VP,Bixby JL,Wittig I,Shah AM,Di Giovanni S

doi

10.1038/s41467-020-20179-z

subject

Has Abstract

pub_date

2020-12-21 00:00:00

pages

6425

issue

1

issn

2041-1723

pii

10.1038/s41467-020-20179-z

journal_volume

11

pub_type

杂志文章

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