Researchers at Nagoya University have identified the range of molecules involved in the regeneration of damaged nerves in roundworms, showing that it largely overlaps with the signals used by the intrinsic removal system to absorb and process dying cells.
The branches of nerve cells called axons are particularly susceptible to damage by the long distances they extend to communicate with each other. In humans, such damage in peripheral parts of the body can be repaired relatively well, but this repair is less effective in the brain and spinal cord, which explains why disorders such as brain and spinal cord injuries are so debilitating.
In a new article published in the journal Nature Communications, researchers at Nagoya University have made significant progress in characterizing the regeneration of axons by studying the nematode Caenorhabditis elegans, a species widely used in biological research and having a very well-characterized nervous system. Specifically, they have shown that axon repair takes place with largely the same set of molecules that mediate the recognition and prolapse of apoptotic (dying) cells by the surrounding cells. The result suggests that this system has been co-opted for an additional goal in the course of evolution.
The team used a laser to cut roundworm axons and then analyzed the next set of molecular reactions that took place. They discovered that this damage resulted in the movement of a lipid called phosphatidylserine (PS) from the inside of the cells to their outside, which was mediated by a protein called an ABC transporter. This externalized PS was then recognized by another molecule, creating a series of reactions that eventually led to repair of the axon. Interestingly, PS is better known as an "eat me" signal that helps the phagocytosis of a dying cell by its neighbors.
"We were able to analyze the complex range of molecules involved in axon repair by using fluorescent labels in and around the cut axon and to overthrow the individual components suspected of being involved," says the corresponding author. Kunihiro Matsumoto. "Although many of these molecules are also active in promoting phagocytosis of apoptotic cells, axon repair provides a" save me "signal instead of a" eat me "signal, which the axons can regenerate. "
The team explains that for the repair of damaged nerves the PS-labeling only appears at the separated locations and only exists for a short time (~ 1 hour), which is in contrast to the labeling when eliminating dying cells that are still long time remaining until the cells are eliminated. The researchers now guess that this difference in signal timing can be a way for the cells to distinguish the meaning of the PS signal – & # 39; eat me & # 39; versus & # 39; save me. & # 39;
According to Naoki Hisamoto, "Now that we know how this system works in the relatively simple roundworm, we should eventually be able to extrapolate the findings to people, which could provide us with a set of goals for pharmaceutical interventions to treat conditions such as brain and injuries. to the spinal cord, where the human body is unable to repair damaged nerves. "