Can Peripheral Nervous System Regenerative Mechanisms be Introduced into the Central Nervous System?

The nervous system in general is not particularly regenerative, but peripheral nervous system tissue is more capable of repair than central nervous system tissue. Focusing on neurons that link these two parts of the nervous system, researchers here report on mechanisms involved in repair of nervous system cells, and propose that it might be possible to make central nervous system cells act more like peripheral nervous system cells in this regard. Whether or not this can be achieved safely is another question, however; this is very early stage work, too early to answer many questions about safety and plausibility.

Neurons in the central nervous system - the brain and spinal cord - and the peripheral nervous system are very similar except in their ability to regenerate. Researchers realized that studying peripheral neurons could help us understand why some damaged neurons regenerate and others do not. They turned to a unique kind of sensory cell that spans both nervous systems. Known as dorsal root ganglion neurons, these cells have long tendrils, called axons, with two offshoots. One branch of the axon connects to cells in the body's periphery and can regenerate if cut; the other side links up with cells in the spinal cord and cannot regrow after injury.

The researchers grew mouse dorsal root ganglion neurons in the lab and then cut them to find out what biological processes occur as the cells regrow their axons. They also cut the sciatic nerve - which runs up the leg and into the spinal cord through the dorsal root ganglia - in mice. The researchers then identified a suite of genes needed to be turned off for the axons to regenerate. "Other people also have shown that a big swath of genes is turned down during regeneration, but as a field we've just said, 'Eh' and ignored them to focus on the genes that are activated. Here, we showed that establishing a regeneration program means some genes have to be turned on but a lot have to be turned off."

In particular, a set of genes related to sending and receiving chemical and electrical signals - the primary duty of mature neurons - had to be silenced for the injury to heal. "The injured neuron has to stop functioning as a neuron and focus on repairing itself. This means the neuron has to transition back to an immature state so it can re-engage developmental programs and regrow." The idea that cells must become less mature in order to regenerate is not new, but the study provides evidence in support of that idea. The researchers identified the key molecular and genetic players involved in regressing to a less mature state, and showed that the timing of the regression was crucial to successful recovery. They are now working on developing a more detailed understanding of when and for how long specific genes must be shut off, and whether silencing the genes in neurons from the central nervous system will induce them to regrow after injury.

Link: https://medicine.wustl.edu/news/regrowing-damaged-nerves-hinges-on-shutting-down-key-genes/

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