Study provides new insight into myelin, mechanisms of MS

July 05, 2023
A new study suggests that myelin, which was previously viewed as a solely protective structure, can actually threaten the survival of the axons. Researchers said the findings suggest that the understanding of multiple sclerosis needs to change.

The exact cause of MS is not yet clear, but a central feature is the loss of an insulating protective layer of axons, the neuronal connections in the central nervous system, which is triggered by autoimmune processes. The coating of the axons, known as myelin, is formed by highly specialized glial cells, oligodendrocytes, and enables the rapid transmission of electrical nerve impulses. 

It has been assumed that, in MS, oligodendrocytes and myelin are degraded by immune cells and the vulnerable axons suffer irreversible damage as a result of further local inflammatory processes. The loss of axons plays a decisive role in the severity of MS in patients and in the course of the disease. This is the case, for example, when myelin sheaths have been attacked by immune cells, but continue to surround the axons and thus isolate them from the environment. 

Oligodendrocytes are not only responsible for the formation of myelin, they also perform important functions that support the energy metabolism of the axons. Myelinated axons, in particular, are highly dependent on metabolic support because they have little access to nutrients on their own. Support of myelinated axons through a myelin sheath requires that the architecture of myelin be intact, including the tight communication channels between the oligodendrocytes and axons.

Researchers from Leipzig University and Max Planck Institute for Multidisciplinary Sciences in Göttingen, Germany, said that when oligodendrocytes are exposed to an acute inflammatory environment, they may lose their ability to support the axons, and myelin becomes a threat to the survival of the axons. To test their hypothesis, the researchers examined tissue samples from patients with MS, as well as various mouse models of MS in order to experimentally simulate the autoimmune attack on myelin. For the first time, the researchers were able to demonstrate by electron microscopy in the tissue samples of the patients that irreversible damage almost always occurs in the axons that are still coated with myelin. Conversely, using genetically modified mouse models, the researchers were able to show that “naked” axons in an acute inflammatory region of the central nervous system are better protected from degeneration. 

Results of animal model studies sometimes do not translate to humans and may be years away from providing a marketable treatment. However, researchers said that by challenging the prevailing image of myelin as a solely protective structure, a deeper understanding of MS can be gained and potentially new treatment strategies developed that will maintain the functionality of the axons. Instead of preserving the damaged myelin, it might actually be therapeutically better to promote rapid degradation of damaged myelin and support the regeneration of functional myelin.

The findings were published in the journal Nature Neuroscience.

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