New hope for CNS damage

It might be possible to reprogram and repair nerves damaged through spinal cord injury and brain trauma say researchers who have identified a mechanism for re-growing fibres in the central nervous system. Injury to axons in the peripheral nervous system (PNS) triggers a coordinated regenerative gene expression programme, but this doesn’t happen in the central nervous system (CNS). Researchers from Imperial College London and the University of Tuebingen carried out systematic epigenetic studies to show that the histone acetyltransferase p300/CBP-associated factor (PCAF) is necessary for nerves to regenerate. “Given that differential regenerative gene expression is associated with regenerative failure in the central nervous system versus regenerative potential in the peripheral nervous system we asked whether an epigenetic code would be responsible for this differential gene expression program and for the regenerative potential,” Professor Simone Di Giovanni, Chair in Restorative Neuroscience at Imperial told Laboratory News. “Systematic investigation pointed to a role for PCAF as responsible to drive the regeneration programme by acetylating specific histone H3 on regenerative genes.” Researchers compared the responses of the PNS and CNS to PCAF in both mouse models and cell culture, and found that epigenetic mechanisms were key to the PNS’s capacity to regenerate. When damaged, nerves send retrograde signals back to the cell body to switch on an epigenetic program to initiate nerve growth. “The results suggest that we may be able to target specific chemical changes to enhance the growth of nerves after injury to the central nervous system,” said Di Giovanni, who is lead author of the paper published in Nature Communications. “The ultimate goal could be to develop a pharmaceutical method to trigger the nerves to grow and repair and to see some level of recovery in patients.” “We are excited about the potential of this work but the findings are preliminary,” he added. “The next step is to see whether we can bring about some form of recovery of movement and function in mice after we have stimulated nerve growth through the mechanism we have identified.” PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system