Nervous system injuries affect over 90,000 people every year, with spinal cord injuries alone estimated to affect 10,000 people each year. As a result of this high incidence of neurological injuries, nerve or neuron regeneration and repair, is becoming a rapidly growing field dedicated to the discovery of new ways to recover nerve functionality after injury. Now, a study from researchers at the National Institute of Neurological Disorders and Stroke shows that boosting the transport of mitochondria along neuronal axons enhances the ability of mouse nerve cells to repair themselves after injury. The team state that their findings suggest potential new strategies to stimulate the regrowth of human neurons damaged by injury or disease. The study is published in The Journal of Cell Biology.
Previous studies show that neurons need large amounts of energy to extend their axons long distances through the body. This energy, in the form of adenosine triphosphate (ATP), is provided by mitochondria, the cell’s internal power plants. During development, mitochondria are transported up and down growing axons to generate ATP wherever it is needed. In adults, however, mitochondria become less mobile as mature neurons produce a protein called syntaphilin that anchors the mitochondria in place. The current study investigates whether this decrease in mitochondrial transport might explain why adult neurons are typically unable to regrow after injury.
The current study shows that when mature mouse axons are severed, nearby mitochondria are damaged and become unable to provide sufficient ATP to support injured nerve regeneration. However, when the lab genetically removed syntaphilin from the nerve cells, mitochondrial transport was enhanced, allowing the damaged mitochondria to be replaced by healthy mitochondria capable of producing ATP. Results show that syntaphilin-deficient mature neurons regain the ability to regrow after injury, just like young neurons, and removing syntaphilin from adult mice facilitated the regeneration of their sciatic nerves after injury.
Data findings show that reduced mitochondrial motility in injured axons is the mechanism controlling regrowth in mature neurons. Results show that severing of an axon induces acute mitochondrial depolarization and ATP depletion in injured axons. The group state that enhancing mitochondrial transport via genetic manipulation facilitated regenerative capacity by replenishing healthy mitochondria in injured axons, thereby rescuing energy deficits. They go on to add that an in-vivo sciatic nerve crush study further shows that enhanced mitochondrial transport in snph knockout mice accelerates axon regeneration.
The team surmise that their study suggests understanding deficits in mitochondrial trafficking and energy supply in injured axons of mature neurons benefits development of new strategies to stimulate axon regeneration. For the future, the researchers state that such combined approaches may represent a valid therapeutic strategy to facilitate regeneration in the central and peripheral nervous systems after injury or disease.