Boosting cellular energy promotes healing of spinal nerves

Every year, up to 500,000 people around the world suffer from spinal cord injuries. Such damage can damage a few, many, or nearly all of the nearby axons (extensions of nerve cells that carry signals up and down the spinal cord between the brain and the rest of the body). . People who survive severe spinal cord injuries often experience lifelong disability.

Adult nerve cells in the spinal cord do not regenerate after injury. Why people don’t do this and how we can encourage them to do so is an area that has been extensively researched. Axons require large amounts of energy to regrow. A team led by Dr. Zu-Hang Sheng of the NIH National Institute of Neurological Disorders and Stroke (NINDS) and Xiao-Ming Xu of Indiana University propose that a lack of energy in damaged nerve cells may contribute to impaired repair and regeneration. did.

Structures called mitochondria provide most of the cell’s energy. In nerve cell axons, mitochondria are held in place by proteins called syntaphilins. When an axon is damaged, this protein prevents mitochondria from migrating to the damaged area.

To test whether manipulating syntaphilin could promote nerve cell repair, the researchers generated mice lacking the protein. They measured whether these mice were better able to recover from three different types of spinal cord injury. This research was partially funded by NINDS. The results were announced on March 3, 2020. cell metabolism.

As expected, injured axons did not regenerate after moderate spinal cord injury in normal mice. Axons in mice lacking syntaphilin were able to regrow beyond the injury site and form functional connections with other neurons. After some types of injury, mice that did not receive syntaphilin showed more recovery in limb dexterity than normal mice. In mice lacking syntaphilin, nearby neurons branched into the injured area one after another, but in normal mice, they did not.

The researchers also observed some axonal regeneration in mice that had undergone severe spinal cord injury and did not receive syntaphilin. However, the lack of the protein alone was not enough to encourage axons to grow beyond the injured tissue. This suggests that other conditions may be required at sites of severe spinal cord injury to promote axonal repair.

The researchers then measured the number and health of mitochondria after spinal cord injury. They found that mice lacking syntaphilin had healthier mitochondria, although they did not have as many mitochondria in their nerve cells as normal mice one week after injury.

To see if directly enhancing energy production could promote axonal repair, the researchers gave mice a compound called creatine after spinal cord injury. Creatine enters the nervous system from the blood and can increase the level of energy produced by mitochondria.

Normal mice given creatine showed some axon regrowth, but most of the new axons did not extend far from the injury. Although the observed repairs were modest, mice given creatine showed improved limb dexterity. Mice lacking syntaphilin showed significant improvement when given creatine.

“These findings support our hypothesis that energy deficit impedes the ability of both the central and peripheral nervous systems to repair after injury,” Sheng says.

The axonal repair seen after creatine administration is not yet substantial, so additional research is needed to identify compounds that more efficiently boost energy in the central nervous system.