When cells of the central nervous system in the brain and spine are damaged by disease or injury, they fail to regenerate, limiting the body’s ability to recover. In contrast, the nerve cells are able to regenerate. Scientists for decades have been looking for clues as to why axons cannot – the fiber-like projections that allow communication between cells of the nervous system to repair themselves after a stroke, bone damage- spine, or traumatic brain injury.
In a large scale of 400 mouse genes, Yale School of Medicine researchers have identified 40 genes that are actively involved in the suppression of axon regeneration in cells of the central nervous system. By editing one of these genes, they were able to restore axons in the ocular nerves of mice damaged by glaucoma.
The findings are reported March 2 in the journal Cell reports.
“This opens a new chapter in regenerative research,” said Stephen Strittmatter, Professor of Neurology Vincent Coates and professor of neuro-science and senior author of the study.
Over the last few decades, Strittmatter and other scientists have discovered a handful of genes that are involved in the regeneration of nervous system cells. But with the advent of RNAs to simulate gene expression and new gene editing technologies capable of removing single genes and measuring their functional impact, that has allowed researchers to expand their search for other culprits. large.
Among the 400 candidate genes previously identified by the Yale team in cultures of cortical neurons, they were able to show that one in 10 of these genes had a direct in vivo effect on axon regeneration in stem cells. the nervous system in mice. One of the 40 genes developed an encoding for an immune system regulator called interleukin-22. Removal of this immune mediator altered the expression of many neuronal regeneration genes and significantly increased axon regeneration in mouse models of glaucoma, they found.
A future study will examine how altering or inhibiting these 40 genes could affect the repair of neurons damaged by stroke and brain and spinal traumatic injuries, Strittmatter said.
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Magazine Reference:
Lindborg, JA, et al. (2021) Optic nerve regeneration screen identifies several genes that limit adult neural repair. Cell reports. doi.org/10.1016/j.celrep.2021.108777.