Unlocking Nerve Regeneration

Schwann cells could be recruited to regenerate damaged axons, by switching on a latent repair program

Signals are transmitted from neurons through axons, which are long spindly projections that connected with nearby cells. Axons are insulated with a fatty substance called myelin, which helps speed up signal transduction and communication, and Schwann cells are responsible for myelination of these connections. New research has discovered that they may also be able to repair nerve connections following injury, and that we may be able to find ways to trigger and enhance this activity to heal crippled axons.

"If you invite Schwann cells to a party, they will clean up the bottles and wash your dishes before they leave the house"

Research at the University of Wisconsin–Madison has determined that Schwann cells appear to switch into a 'housekeeping' form following an injury; clearing up myelin inhibiting regeneration and regrowth. While myelin is essential for normal nerve function it actually impairs regrowth, and once in 'housekeeping' mode, Schwann cells unravel their previous work by dissolving this myelin and encouraging recovery. These cells also appear to secrete signals to attract blood cells to help, as well as laying out a map for regrowth and finally re-myelinating the axon later on. 

"We saw a set of latent genes becoming active, but only after injury, and these started a program that places the Schwann cells in a repair mode where they perform several jobs that the axon needs to regrow"

An epigenetic switch

When the researchers examined the cells closer, they found to their surprise that these cells weren't regressing to a more primitive, stem cell like form before they changed their function. Most recovery processes in the brain require stem cells, but activated Schwann cells were changing their behaviour by regulating their genes differently - tampering with the epigenetic controls on their genome. They were essentially being directly reprogrammed. 

"Almost every other nervous-system injury response, especially in the brain, is thought to require stem cells to repopulate the cells, but there are no stem cells here. The Schwann cells are reprogramming themselves to set up the injury-repair program. We are starting to see them as active players with dual roles in protecting and regenerating the axon, and we are exploring which factors determine the initiation and efficacy of the injury program"

On further examination the team identified a molecular switch called PRC2 which normally silences this housekeeping program and maintains normal function. Finding ways to trigger this system could therefore possibly boost recovery in injured patients; allowing us to better control and kickstart the process.  They also discovered an enzyme that may directly act on this switch, but more work is needed to determine its effect. Many factors effect axon repair, and this study focused on peripheral nerve recovery rather than the connections in the brain and spinal cord which are maintained by a different type of cell. However, the discovery is another reminder that we still have a great deal to learn about our own biology, and could lead to improved treatment in peripheral nerve injury. 

Read more at MedicalXpress