Fig. 1. Different responses of the DRG neurons to dorsal column axotomy (DCA) and sciatic nerve axotomy (SNA).

The axonal injury to the sciatic nerve induces specific signaling that activates the transcription of regeneration associated genes (RAGs) in the DRG neurons by harmonizing the function or activity of epigenetic regulators such as histone deacetylases (HDACs) and histone acetyltransferases (HATs), leading to a “regeneration program” being switched on. Transcription factors such as p53 and Smad1 can initiate gene transcription to promote regeneration after epigenetic changes take place. Most of the regulatory processes involved in epigenetic modulation fail to occur in the DRG neurons after DCA in the central nervous system. Due to this failure, an axonal injury in the central branch tends to be characterized by weak activation of the gene transcription required for a robust regeneration program, leading to regeneration failure in the central nervous system. The use of HDAC inhibitors in pharmacological applications to activate the epigenetic regulation of DRG neurons by enhancing the levels of histone acetylation has been reported. Green ellipse: histone complex. Green ellipse with a red triangle: post-translationally modified histone complex. HDACs: histone deacetylases. HATs: histone acetyltransferases. TFs: transcription factors. DCA: dorsal column axotomy. SNA: sciatic nerve axotomy. RAGs: regeneration-associated genes.