Fresh insights into how zebrafish repair their damaged nerve connections could aid the development of therapies for people with spinal cord injuries.
Scientists have found the immune system plays a key role in helping zebrafish nerve cells to regenerate after injury.
The findings offer clues for developing treatments that could one day help people to regain movement after spinal cord injury.
Large immune cells called macrophages but not neutrophils or microglia are vital for the fish to repair damaged connections, the study found. These cells usually help the body to fight off infections but they also play a key role in wound healing.
Researchers found macrophages produce key molecules that dampen inflammation at the spinal injury site. This enables nerve cells to bridge the gap and repair lost connections. Macrophage-less irf8 mutants show prolonged inflammation with elevated levels of Tnf-α and Il-1β. Inhibiting Tnf-α does not rescue axonal growth in irf8 mutants, but impairs it in wildtype animals, indicating a pro-regenerative role of Tnf-α.
In contrast, decreasing Il-1β levels or number of Il-1β+ neutrophils rescue functional regeneration in irf8 mutants. However, during early regeneration, interference with Il-1β function impairs regeneration in irf8 and wildtype animals. Hence, inflammation is dynamically controlled by macrophages to promote functional spinal cord regeneration in zebrafish.
The team has established a system to study the complex interactions between immune cells at a spinal injury site and how they contribute to the repair of damaged nerve connections in zebrafish.
The next step will be to understand how these molecules function in people. The study was published in Nature Communications.