Discovered a fundamental mechanism to repair damaged nerves

Spontaneous repair of peripheral nerves is possible thanks to Schwann cells. / Pixabay

Unlike what happens with the spinal cord after an injury, the peripheral nerves – which innervate the muscles and make their movement possible have a significant ability to ‘self-repair’. However, it is a slow process that can fail and leave sequels. Neurosciences Institute of Alicante have taken an important step to facilitate this repair process.

After an injury, the final part of the peripheral nerves undergoes a specialized biological process with the aim o creating the right conditions for its regeneration. Finding out how this repair is carried out is important to shorten the recovery and intervene when it does not occur properly. In addition, it could contribute to understanding what fails in the central nervous system and achieve the long-sought after goal of repairing the spinal cord after an injury.
Spontaneous repair of the peripheral nerves is possible thanks to a special type of cells, called Schwann cells. They wrap the nerve fibers with an insulating layer, myelin, and this fat layer protects the nerves and considerably increases the speed of transmission of nerve impulses.
In the Institute of Neurosciences of Alicante, mixed center of the Miguel Hernández University of Elche and the CSIC, the group of Hugo Cabedo has just discovered precisely how the damaged nerve induces the production of the myelin layer by the Schwann cell, after an injury, so that communication is restored correctly.
Finding out how nerve repair is done can shorten recovery and intervene when it does not occur properly
“In the peripheral nervous system Schwann cells play a very important role through a highly regulated process of differentiation and dedifferentiation, a characteristic that no other cell of the nervous system has. This makes them very plastic and allows them to move from a state in which they produce myelin to another, less differentiated, in which they contribute to repair the damaged nerve, “explains Cabedo.
When we suffer an injury to a peripheral nerve, such as the one that goes from the medulla to the fingers of the hand or the foot, these cells temporarily lose the capacity to form myelin and go back to a very de-differentiated anterior stage.

The goal of this transformation is to help the nerve regenerate and reach the target tissues. Once the nerve is repaired, the cell recovers its capacity to produce myelin to cover the nerve with the insulating layer and allow the correct transmission of nerve impulses. Although this process of changing the state of Schwann cells is known, it was not clear how it is carried out.

The group of Cabedo has found out that in this process a chemical messenger called cyclic AMP plays a fundamental role. “The cyclic AMP sends the nucleus of the Schwann cells to a protein called histone deacetylase 4 which, once the nerve is repaired, starts the myelination again. This is achieved by inactivating the c-Jun gene, which under normal conditions blocks the production of myelin. This blockage of the c-Jun gene is necessary and sufficient to activate the myelin-producing genes and to start again the Schwann cell differentiation program to coat the regenerated nerve. “

This process is what makes possible the spontaneous repair of a nerve or in some cases reimplantar an amputated finger, for example. “If you cut a peripheral nerve and the surgeon stitches it properly it ends up regenerating. Although the nerves in their terminal part degenerate, the Schwann cells, which are maintained, now become restorative and help the nerve to reach the target tissues again. Once the nerve has reached its destination, the Schwann cell again becomes a myelin producer to add the insulating layer and thus recover the ability to move and touch. Unfortunately in nerves of a certain entity, nerve regeneration and associated clinical evolution is not complete, leaving sequels for life, “explains Cabedo.

This finding may facilitate the treatment of peripheral nerve injuries, such as in traffic accidents. “This is the next step of our investigation”, highlights this expert.

Diseases that deteriorate myelin

The finding may also be important to improve the treatment of some diseases in which myelin deteriorates, such as Charcot Marie Tooth, of genetic origin, in which “Schwann cells lose myelination capacity and coordination problems appear in the legs, with trips, falls, atrophy of the muscles and serious difficulties to walk “, Cabedo points out.

It may also be relevant in Guillain-Barré syndrome, a neurological disorder that occurs after an infection, and in which the immune system suddenly attacks Schwann cells. This has very serious consequences, which include the loss of mobility and the ability to perceive external stimuli. In addition, there is a progressive respiratory deficit that can lead to death by asphyxia in one or two days if you do not act quickly to provide assisted breathing in an intensive care unit.

“The research we are carrying out can also help to design therapies that improve remyelination after the autoimmune attack that takes place in Guillain-Barré syndrome,” the expert points out.

Other studies suggest that myelin is also altered in Alzheimer’s disease and in schizophrenia. “It is therefore foreseeable that new work aimed at understanding how myelin is formed can help clarify the causes of these diseases,” he concludes.

Bibliographic reference:

Gomis-Coloma C, Velasco-Aviles S, Gomez-Sanchez JA, Casillas-Low A, Backs J, Cabedo H. Class IIa histone deacetylases link cAMP signaling to the myelin transcriptional program of Schwann cells. J Cell Biol. 2018 doi: 10.1083 / jcb.201611150.

Geographical area: Spain
Source: Institute of Neurosciences of Alicante and Sinc Agency