This is a lay abstract of our article published on Biorxiv on May 25th, 2020 titled "New oligodendrocytes exhibit more abundant and accurate myelin regeneration than those that survive demyelination".
Background
Myelin, a fatty protein which envelops and protects nerve cells, is affected in many nervous system disorders including multiple sclerosis (MS). Here, the immune system attacks myelin, which can cause both myelin-producing cells and nerve cells to die.
Thankfully, our brains have some capacity to replace lost myelin, in a process called remyelination. Researchers hope to enhance this process in order to treat diseases like MS, but to do so, we need to better understand the cells responsible for remyelination.
New myelin is made by cells called oligodendrocytes. When oligodendrocytes die, new ones can be made to take the place of those that were lost; most remyelination therapies try to reinforce this process. However, recent research showed that oligodendrocytes that survive myelin loss may also be able to make new myelin. This raises the possibility of boosting remyelination by encouraging such surviving oligodendrocytes to replace lost myelin.
Study
Previous studies were unable to directly compare newly-made and surviving oligodendrocytes. We set out to address this problem by making a new zebrafish model of myelin damage. Since zebrafish are transparent, we can look at both surviving and newly-made cells as they regenerate myelin over time.
Results
We found that following myelin damage, remyelination by newly-made cells was much more efficient than remyelination by surviving cells. New oligodendrocytes were made within a few days of myelin damage, and rapidly produced abundant myelin to replace what was lost.
In contrast, surviving oligodendrocytes made very little myelin, and surprisingly, the little they made was often on the wrong areas of nerve cells. Using a drug, we tried to boost the capacity of survivors to make new myelin, but this treatment only increased the amount of misplaced myelin.
We were particularly intrigued by the fact that surviving cells made myelin in the wrong locations, since this hadn’t been described before. In collaboration with Anna Williams’ lab, we studied the post-mortem brain tissue of people with MS. In areas of remyelination in the brain, we found misplaced myelin similar to what we had seen in the zebrafish. In other words, we have found a new feature of oligodendrocytes in MS: their tendency to target myelin inappropriately.
Impact
Better understanding remyelination will help us to improve the treatments of myelin diseases, such as MS. We directly compared surviving and newly-made oligodendrocytes in a new zebrafish model of myelin damage, showing that new oligodendrocytes have a much greater capacity for remyelination than survivors. Therefore, our study suggests that the best strategy to promote myelin repair is to boost the production and remyelination capacity of new oligodendrocytes.