Genome

Back to Basics: Neurons May Heal Spinal Cord Injury By Reverting to a Younger State

Posted on 1 May 2020

In response to injury, neurons may be able to revert their gene expression back to a developmental state, thereby allowing tissue to be repaired as new connections are formed.

Injury to the central nervous system was once thought to be essentially irreparable, due to the complexity of connections between neurons and the inability of more specialised cells to divide and produce new cells. While the brain and spinal cord cannot heal themselves effectively, previous research has shown that in mice, the corticospinal tract can in fact be regenerated by grafting stem cells called neural progenitor cells to the site of injury.

In the current study, researchers wanted to investigate what was happening on a molecular level during this repair process. To do this, they studied the gene expression in motor neurons of mice after spinal cord injury. They found 365 genes with increased levels of expression after spinal cord injury compared with the uninjured controls. However, in mice that did not receive grafts of neural progenitor cells, the expression levels of these genes decreased after two weeks, whereas those receiving grafts maintained their expression levels.

Image of regenerating neurons (green) wihin a section of the cortex follwing injury
Poplawski, G., Kawaguchi, R., Van Niekerk, E., Lu, P., Mehta, N., & Canete, P. et al. (2020). Injured adult neurons regress to an embryonic transcriptional growth state. Nature. doi: 10.1038/s41586-020-2200-5

Of particular interest, however, was that the genes showing increased expression were mainly involved in the development of infant cells into mature neurons. In other words, the injured neurons reverted to a younger state, which may have allowed them to become more plastic and form new connections during the repair process.

When an adult brain cell of the cortex is injured, it reverts (at a transcriptional level) to an embryonic cortical neuron. And in this reverted, far less mature state, it can now regrow axons if it is provided an environment to grow into. In my view, this is the most notable feature of the study and is downright shocking.

Mark Tuszynski, MD, PhD, professor of neuroscience and director of the Translational Neuroscience Institute at UC San Diego School of Medicine
If damaged, the adult brain repairs itself by going back to the beginning — Sott.net. (2020). Retrieved 1 May 2020, from https://www.sott.net/article/432810-If-damaged-the-adult-brain-repairs-itself-by-going-back-to-the-beginning

This finding was not the only surprise for the researchers: they also identified the developmental gene huntingtin as being central to this regenerative process. Mutations in the huntingtin gene are associated with Huntington’s disease, a brain disorder that breaks down neurons and leads to loss of motor control. In this study, not only was the huntingtin gene active in regenerating neurons, but deletion of the gene reduced regeneration by 60%.

While a lot of work has been done on trying to understand why Huntingtin mutations cause disease, far less is understood about the normal role of Huntingtin. Our work shows that Huntingtin is essential for promoting repair of brain neurons. Thus, mutations in this gene would be predicted to result in a loss of [the ablilty of] the adult neuron to repair itself. This, in turn, might result in the slow neuronal degeneration that results in Huntington’s disease.”

Mark Tuszynski, MD, PhD, professor of neuroscience and director of the Translational Neuroscience Institute at UC San Diego School of Medicine
If damaged, the adult brain repairs itself by going back to the beginning — Sott.net. (2020). Retrieved 1 May 2020, from https://www.sott.net/article/432810-If-damaged-the-adult-brain-repairs-itself-by-going-back-to-the-beginning

This study not only advances our understanding of the central nervous system’s repair process, but may also lead to a better understanding of the pathology behind Huntington’s disease.


References

Injured adult neurons regress to an embryonic transcriptional growth state: https://doi.org/10.1038/s41586-020-2200-5

Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration: doi: 10.1038/nm.4066

Brain Cells Get Younger To Heal Spinal Cord Injuries: https://sciworthy.com/brain-cells-get-younger-to-heal-spinal-cord-injuries/

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