Multiple sclerosis (MS): Cholesterol crystals prevent regeneration in the central nervous system

Lipid metabolism controls regeneration in the central nervous system.

Multiple sclerosis: Cholesterol crystals prevent regeneration in the central nervous system
Together with his team Prof. Mikael Simons researches the formation and removal of the myelin sheathes which surround nerve fibers and which are destroyed in Multiple Sclerosis. (Photo: A. Eckert / TUM)

Multiple Sclerosis (MS) is an interminable provocative disease of the central nervous system, in which the body’s own immune cells assault the greasy, protecting myelin sheath encompassing nerve strands. The recovery of in-place myelin sheaths is vital for patients to recoup from MS relapses. In any case, the body’s capacity to recover myelin diminishes with age.

Scientists the Technical University of Munich (TUM) has now a possible explanation: Fat derived from myelin, which is not carried away rapidly enough by phagocytes can trigger chronic inflammation that in turn impedes regeneration. Moreover, in a moment distribution, Simons’ group depicts the revelation of novel cell write, which seems just when a myelin sheath is being made.

The myelin sheath assumes a conclusive part in the capacity of the focal sensory system: it is a particular film enhanced in lipids, which protects nerve strands with the goal that electrical signs can be passed on rapidly and effectively. In MS, there is a multifocal immune system assault against the myelin sheath in the focal sensory system, which causes neurological shortages, for example, loss of engine work. Recovery of myelin is conceivable, however, in MS it is insufficient.

One reason is probably incessant irritation happening in the sores. A group drove by TUM Molecular Neurobiology teacher Mikael Simons has now found that after the annihilation of myelin crystalline cholesterol can trigger constant irritation which anticipates recovery, comparable to in arteriosclerosis.

Prof. Simons said, “Myelin contains a very high amount of cholesterol. When myelin is destroyed, the cholesterol released has to be removed from the tissue. This is performed by microglia and macrophages, also referred to as phagocytes. They take up the damaged myelin, digest it and transport the non-digestible remainder, such as cholesterol, out of the cell by transport molecules.”

“However, if too much cholesterol accumulates in the cell, cholesterol can form needle-shaped crystals, which cause damage the cell. Using a mouse model, Simons and his team showed the devastating impact of the crystalline cholesterol: It activates the so-called inflammasome in phagocytes, which results in the release of inflammatory mediators, attracting even more immune cells. Very similar problems occur in arteriosclerosis, however not in the brain tissue, but in blood vessels.”

How well the microglia and macrophages did their activity was at last additionally subject to the age of the creature: the more established the creature, the less powerful was the leeway of cholesterol and the more grounded the perpetual irritations.

“When we treated the creatures with a pharmaceutical that encourages the vehicle of cholesterol out of the cells, aggravation diminished and myelin was recovered,” says Mikael Simons. Next, he and his group need to research whether this system can be utilized restoratively to advance recovery in MS.

Through this study, scientists have discovered a novel oligodendroglial cell type. Oligodendrocytes are specialized glial cells that are responsible for myelination in the central nervous system.

Mikael Simons said, “We believe that the BCAS1-positive oligodendrocytes that we discovered represent an intermediate stage in the development of myelin-forming cells. In humans, they can only be identified for a relatively short period of time, exactly then when myelin is actually being formed.”

“In the human brain, for example, they are found in newborns, which generate myelin at a high rate. In adults, these cells disappear, but they can be re-formed when myelin has been damaged and needs to be regenerated.”

“We hope that the BCAS1 positive cells will help us to identify new regenerative medicines. We can now rapidly screen for drugs that promote the formation of these cells, he adds. Furthermore, they could be used to get a better understanding of exactly when and how myelin is created during the course of a human life.”

The study is now published a possible explanation in the journal “Science”.