Supplementary Materials

The PDF file includes:

  • Fig. S1. Exposure to EE enhances neurite outgrowth on inhibitory myelin substrate to a similar extent as a conditioning SNA injury.
  • Fig. S2. Inhibiting transcription with actinomycin-D blocks the EE-mediated increase in DRG neurite outgrowth.
  • Fig. S3. Exposure to EE enhances axon elongation rather than branching.
  • Fig. S4. The full EE increases DRG neurite outgrowth compared to the running wheel alone.
  • Fig. S5. Exposure to EE enhances muscle reinnervation by proprioceptive DRG neurons.
  • Fig. S6. EE promotes axon regeneration and the formation of putative synapses.
  • Fig. S7. Neurotrophin and cytokine levels in the DRG and blood serum are not affected by EE.
  • Fig. S8. RNA-seq and proteomic datasets demonstrate that EE strongly modulates pathways involved in neuronal activity, calcium signaling, gene expression, and cytoskeletal changes.
  • Fig. S9. Efficient transduction and DREADD expression in PV-positive DRGs.
  • Fig. S10. The EE-mediated increase in DRG neurite outgrowth is mediated by neuronal activity.
  • Fig. S11. H3K27ac is increased in PV-positive DRGs after exposure to EE, but the levels of H3K4me2, H3K9ac, and H3K4me3 do not change compared to SH.
  • Fig. S12. Levels of H4K8ac but not of acCbp or pCreb remain elevated in PV-positive DRGs for 5 weeks after exposure to EE.
  • Fig. S13. Increasing neuronal activity augments the level of H4K8ac and acCbp in DRG neurons.
  • Fig. S14. The CaMKIIa promoter is active in DRG neurons and drives strong expression of tdTomato after tamoxifen treatment.
  • Fig. S15. CSP-TTK21 treatment significantly enhances the time to remove adhesive tape placed on the hindpaw.
  • Fig. S16. CSP-TTK21 treatment promotes sprouting of afferent fibers below the level of injury.
  • Fig. S17. CSP-TTK21 treatment enhances H4K8ac in the DRG.
  • Fig. S18. CSP-TTK21 treatment does not affect the glial scar after a thoracic dorsal spinal cord hemisection in mice.
  • Fig. S19. List compiling the 78 parameters used for quantifying gait features.
  • Fig. S20. CSP-TTK21 reduced the number of slips during locomotion along a horizontal ladder.
  • Fig. S21. CSP-TTK21 treatment enhances levels of H4K8ac in the raphe nucleus and reticular formation.
  • Fig. S22. CSP-TTK21 treatment does not affect the glial scar after a thoracic contusion SCI in rats.
  • Legends for movies S1 to S3
  • Legends for data files S1 to S3
  • References (5558)

[Download PDF]

Other Supplementary Material for this manuscript includes the following:

  • Movie S1 (.mp4 format). EE-mediated calcium mobilization in proprioceptive DRG neurons.
  • Movie S2 (.mp4 format). SH-mediated calcium mobilization in proprioceptive DRG neurons.
  • Movie S3 (.mp4 format). Treatment with CSP-TTK21 enhances hindlimb function and over-ground locomotion.
  • Data file S1 (Microsoft Excel format). Differentially expressed genes and proteins after EE compared to SH.
  • Data file S2 (Microsoft Excel format). Functional classification of EE-dependent gene expression changes.
  • Data file S3 (Microsoft Excel format). Raw data.