In a study published recently in the journal Nature Communications, scientists report the discovery of a system that regulates the regeneration of damaged nerves, which may represent a novel target for research into the treatment of spinal cord injuries.
The nervous system is broadly divided into two parts; the peripheral nervous system (PNS) and the central nervous system (CNS). The peripheral nervous system consists of the nerves outside of the brain and spinal cord, and serves to connect the CNS to limbs and organs by relaying information to and from the brain. The CNS on the other hand consists of the brain and spinal cord and acts as a processing center, integrating sensory information and coordinating an appropriate response. When the PNS is injured, a coordinated gene expression program is triggered which results in the regeneration of the damaged nerve cells. On the contrary, when the CNS is damaged the nerves are incapable of regeneration; this is a major cause of neurological impairment following CNS injury. This means that currently spinal cord injuries are largely irreparable. Spinal cord injuries, for example due to major trauma from an accident, disrupt the relay of information between certain parts of your body and your brain, and may therefore result in paralysis.
Why the PNS, but not the CNS, is capable of coordinating a system that results in the regeneration of damaged nerves was the central question for the researchers who carried out this study. It was hoped that this knowledge could be applied to CNS injuries, possibly offering a way to help individuals not only with spinal cord injuries but also brain injuries and those who have suffered a stroke.
The researchers discovered that the key to PNS regeneration lay in epigenetics. The cells that make up the body have identical DNA sequences, yet they have different characteristics (phenotypes). For example liver cells are different to neurons, yet they contain the same genetic material. This means that genetic sequences alone cannot explain how some cellular traits are propagated- this is where epigenetics comes in. Epigenetics involves genetic control by factors other than the sequence of DNA, which results in the switching on or off of certain genes in response to the environment.
The study revealed that the scientists found the previously unknown link between injury and repair gene activation. They did this by tracking how the signals initiated by injury in PNS neurons communicate that genes involved in regeneration should be activated. It was discovered that a protein called PCAF promotes key regeneration-associated genes following peripheral but not central nerve injury, which ultimately allows these peripheral nerves to repair. When this PCAF protein was injected into mice with CNS damage, the number of nerve fibers that grew back was significantly increased. This suggested that it is possible to chemically control the regeneration of damaged CNS nerves.
Although this research is very much in its infancy, it may pave way to the eventual development of a drug that can stimulate CNS nerves to repair in a similar manner to how PNS nerves regenerate. But first, the scientists need to discern whether this PCAF-dependent mechanism of nerve repair can recover any movement or function in CNS damaged mice.
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