Cbp-dependent histone acetylation mediates axon regeneration induced by environmental enrichment after spinal cord injury in rodents

After a spinal cord injury (SCI), motor and sensory axons fail to regenerate, leading to permanent neurological impairments. The absence of regeneration in the central nervous system (CNS) after injury has been attributed to growth inhibitory molecules and the lack of an effective neuronal-intrinsic regenerative response. The study found that placing mice in an enriched environment prior to an injury enhanced the activity of proprioceptive dorsal root ganglion neurons leading to a lasting increase in their regenerative potential. This effect was dependent on Creb-binding protein (Cbp) mediated histone acetylation. The researchers administered a small molecule activator of Cbp, which promoted regeneration and sprouting of sensory and motor axons, and also the recovery of sensory and motor functions in both mouse and rat models of spinal cord injury.

• 1
  Environmental enrichment (EE) enhances the regenerative potential of DRG neurons in mice, leading to increased neurite outgrowth and axonal regeneration after SCI.
• 2
  The EE-dependent increase in regenerative potential is contingent on intact proprioceptive afferent feedback and involves increased neuronal activity and calcium signaling in proprioceptive DRG neurons.
• 3
  Cbp-mediated histone acetylation is required for the EE-dependent increase in regeneration potential, and pharmacological activation of Cbp/p300 promotes sensory axon regeneration and functional recovery after SCI in mice and rats.