Platelets in Remyelination: Not Too Much, Just at the Right Time.

Myelin is an insulating structure that wraps around axons, allowing the fast and efficient transmission of electrical impulses and ensuring proper neurological function. In the central nervous system (CNS), myelin is produced by oligodendrocytes. During multiple sclerosis (MS), myelin is destroyed, leading to neurological deficits. Even though myelin can be restored through a process known as remyelination, this regenerative response largely fails in MS. Why?

We know platelets as tiny circulating cells in the blood. Platelets are fundamental in the process of blood coagulation. In addition, platelets contain molecules that participate in inflammation and tissue repair. Yet, there are even more fascinating functions associated with them waiting to be revealed. Do platelets support remyelination? Platelet abnormalities have been described during MS. For example, in MS patients, platelets are hyperactive, and besides the loss of myelin, lesions in the brain and spinal cord show signs of platelet accumulation. Do platelet abnormalities observed in MS patients contribute to remyelination failure?

In a recent study published by our laboratory in the journal eLife (), we aimed to study whether and how platelets are involved in remyelination. First, we observed that in response to myelin damage, platelets transiently accumulated in the lesions but later disappear and remyelination successfully occurred. Interestingly, animals with low numbers of circulating platelets (thrombocytopenia) showed a reduction in the generation of new oligodendrocytes and myelin regeneration failed. Oligodendrocyte progenitor cells (OPCs) are the major source of newly formed myelinating cells in the CNS. Thus, we studied in vitro platelets - OPCs interactions. Consistent with these observations, we noticed that a short exposure (pulse) to platelets boosted OPC differentiation and the generation of oligodendrocytes. However, when OPCs were sustainedly exposed to platelets, this effect was suppressed. Finally, a sustained increase in the number of circulating platelets (thrombocytosis) led to a persistent accumulation of these cells in the lesions (such as occurs in MS), followed by a reduction in the number of remyelinating oligodendrocytes.

In conclusion, our study extends the function of platelets to include myelin regeneration. Our findings indicate that platelets support remyelination; however, their abnormalities may lead to remyelination failure. While transient exposure to platelets aids OPC differentiation, sustained exposure alters the generation of new oligodendrocytes. The platelet-derived molecules and the underlying mechanisms by which platelets exert this bimodal influence on OPC function and remyelination remain to be identified and elucidated, respectively. This study provides the first insights and hints on how platelets may be involved in remyelination failure during MS.

Text by: Carlos Valenzuela, PhD Student and Francisco J. Rivera (TReN).