Multiple sclerosis: The phagocytes are overwhelmed in old age

A newly discovered cell type gives hope for better multiple sclerosis therapies

Scientists have apparently investigated the reason why regeneration phases in patients with relapsing multiple sclerosis occur less and less with increasing age. Relapsing-form multiple sclerosis leads to acute attacks of illness, which can cause nerve damage and disabilities. During the breaks between these attacks, the body has time to regenerate. However, with age, these breaks become shorter and shorter and the autoimmune disorder worsens continuously.

The research team led by Mikael Simons from the Max Planck Institute for Experimental Medicine in Göttingen, Germany, was able to show in a study of mice with nerve lesions that resemble multiple sclerosis that with increasing age the mice are less and less able to replace the damaged myelin sheaths of the nerve cells . The phagocytes, also called microglia and macrophages, were responsible for this process. These are responsible for the removal of residual products. With advancing age, the phagocytes increasingly had problems "disposing" of the residual products of the damaged nerve cells. The results of this study were published in two publications in the journal Science.

What happens in a multiple sclerosis attack?

In the chronic inflammatory disease of the central nervous system multiple sclerosis (MS), immune cells break down the fat-rich myelin sheaths of the nerve cells. The myelin sheaths play a crucial role in the functioning of the central nervous system. The particularly fat membrane isolates the nerve fibers so that electrical signals can be passed on quickly and efficiently. If this membrane is damaged, affected people can experience symptoms of failure such as paralysis. After an MS attack, the intact myelin sheaths rebuild and the patients recover. But the ability to regenerate decreases with age.

The regeneration of myelin sheaths - a vicious cycle?

The researchers were able to document that fat molecules from the myelin sheath can trigger chronic inflammation if they are no longer removed quickly enough. "Myelin has a very high proportion of cholesterol," explains Professor Simons in a press release from the Technical University of Munich. If myelin is destroyed, the cholesterol released in the process must be removed from the tissue. Eating cells, also called microglia and macrophages, are responsible for the removal. They would absorb the damaged myelin sheath inside the cell, digest it and transport the indigestible remnants out of the cell via transport molecules. If too many fat molecules accumulate in a short time, crystal formation can occur. This can have devastating effects on the phagocytes, which activate a so-called inflammasome as a result of crystal formation, which in turn leads to more immune cells being attracted.

Regeneration decreases with age

The scientists were able to show in mice that the phagocytes grew more and more poorly as they grew older. The older the mice, the poorer the cholesterol removal and the greater the chronic inflammation. "If we treated the animals with a drug that promotes the removal of cholesterol, the inflammation decreased and the myelin sheaths were regenerated," explains Mikael Simons. The scientists now want to investigate whether this mechanism is suitable for therapies in MS patients to accelerate regeneration.

Further findings from the study

The scientists also discovered a new cell type in the study. It is a special form of the so-called oligodendrocytes. These are among the glial cells in the brain that are responsible for myelination. "We assume that the BCAS1-positive oligodendrocytes we discovered represent an intermediate stage in the development of these cells," reports Mikael Simons. They can only be detected for a relatively short time when myelin is formed. While these cells are particularly strong in newborns, they largely disappear in adults. According to the scientists, however, they reappear when myelin sheaths are damaged and need to be rebuilt. "We hope that the BCAS-1 positive cells can help us find new drugs to regenerate myelin," said Simons. (vb)

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Video: Misdiagnosed: My MS Symptoms Were Dismissed as Stress. Health (December 2021).