How to help regenerate the processes of neurons
The key to axon restoration has been found
Nanonews Network based on materials from Washington University School of Medicine: Scientists identify clue to regrowing nerve cellsScientists from Washington University School of Medicine in St. Louis have identified a chain reaction responsible for repairing damaged axons - a discovery that could significantly help in the development of effective treatments for nerve damage leading to loss of sensitivity or paralysis.
An article about the study was published in the journal Cell (Cho et al., Injury-Induced HDAC5 Nuclear Export Is Essential for Axon Regeneration).
In addition, American researchers have proved that one of the links of this chain reaction in the nerve cells of both the brain and spinal cord is lost. The loss of this link, the HDAC5 protein, may explain why these cells do not show the ability to independently restore lost appendages. A new study suggests that the activation of HDAC5 in the central nervous system may trigger the regeneration of nerve cell processes.
"We knew that several genes contribute to the restoration of the processes of these nerve cells, called axons, but what activates the expression of these genes, and hence the recovery process, has remained unknown until now," says the head of the study Valeria Cavalli, PhD, associate professor of the Department of Neurobiology. "Our discovery brings us closer to the fact that one day we will be able to develop treatments that make axon regeneration more effective."
Axons are the processes of nerve cells that send messages. As a rule, they are much longer and more susceptible to damage than dendrites that perform another function – receiving messages.
In the peripheral nervous system – a network of nerve cells outside the brain and spinal cord – the regeneration of damaged axons sometimes occurs naturally, which, unfortunately, cannot be said about the central nervous system, where damaged axons, as a rule, are not restored.
Working with cells of the peripheral nervous system grown in the laboratory, Yongcheol Cho, PhD, a researcher in Dr. Cavalli's laboratory, cut off parts of axons. As it turned out, this causes a wave of calcium movement along the remaining part of the axon to the cell body. This wave is the first stage of a cascade of reactions that activate the mechanisms of regeneration of the process.
To study the reaction of nerve cells to damage to their axons, scientists at the University of Washington
they are grown in the form of "spots" resulting from the treatment of the cell surface with specific antibodies.
(Photo: Yongcheol Cho, PhD)In the cells of the peripheral nervous system, one of the most important links of this chain reaction is the release of the HDAC5 protein from the central compartment of the cell – its nucleus.
As the researchers found, after leaving the nucleus, HDAC5 activates a number of genes involved in the regeneration process. In addition, HDAC5 migrates to the site of injury, where it participates in the synthesis of microtubules – rigid support structures that help recreate the architecture of the regenerating axon.
Diagram from the article in the Cell – VMWhen the researchers modified the HDAC5 gene in such a way that its protein could not escape from the nuclei of peripheral nerve cells, axons in cell cultures were not restored.
At the same time, treatment of axons growing in culture with drugs that help HDAC5 leave the nucleus stimulated regeneration. The results of these experiments were reproduced in animal experiments.
Scientists observed a completely different picture when studying the same chain reaction in the cells of the central nervous system: HDAC5 never left the nucleus and did not migrate to the site of damage. According to the researchers, the inability of HDAC5 – the most important actor in this "play" – to exit the nucleus may be one of the main reasons for the lack of regeneration of axons of cells of the central nervous system.
"The results of our study can be considered very encouraging. If we manage to find ways to manipulate this system in the neurons of the brain and spinal cord, we will be able to help the cells of the central nervous system in restoring the lost processes," Dr. Cavalli sums up. "That's what we're working on right now."
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