The expression of histone deacetylases and the regenerative abilities of spinal-projecting neurons after injury.

Abstract

Epigenetic control of regeneration after spinal cord injury: Complete spinal cord injury (SCI) in humans and other mammals leads to irreversible paralysis below the level of injury, due to failure of axonal regeneration in the central nervous system (CNS). Previous work has shown that successful axon regeneration is dependent upon transcription of a large number of regeneration-associated genes (RAGs) and transcription factors (TFs) (Van Kesteren et al., 2011). A prominent theory in the field of axon regeneration is that the large differences in regenerative potential between peripheral nervous system (PNS) neurons, which regenerate well, and CNS neurons, which do not, reflect differences in intrinsic transcriptional networks, rather than individual genes (Van Kesteren et al., 2011). These injury-inducible TFs are presumed to control hundreds of transcriptional targets of multiple regeneration-associated signaling pathways (Van Kesteren et al., 2011). Thus the seeming intractability of CNS axon regeneration might be due to the need to simultaneously turn on or off multiple regeneration-associated signaling pathways. One strategy to promote axon regeneration after SCI is to activate this TF “master switch” and enhance the axon growth capacity in adult neurons. Thus far, no such TF “master switch” has been found and it is possible that epigenetic modifications function as “master switches” that regulate transcription of RAGs after SCI, and thus activate or suppress entire regeneration-promoting pathways.