Stopping Thrombin’s Release in Brain May Prevent Myelin Loss in Diseases Like MS, Mouse Study Suggests

Myelin loss might be prevented by astrocytes, a brain cell that regulates myelin’s thickness in coating nerve fibers to support the proper transmission of nerve signals, after astrocytes were seen to block an enzyme called thrombin in a study from the National Institutes of Health (NIH).

Its researchers suggest that approved medications to inhibit thrombin might work to stabilize myelin and possibly slow or stop its loss in diseases like multiple sclerosis (MS). They are now testing this hypothesis in mouse models of MS.

The study, ”Regulation of myelin structure and conduction velocity by perinodal astrocytes” was published in the journal Proceedings of the National Academy of Sciences of the United States of America.

Myelin, the fat-rich substance that wraps around nerve fibers (axons), works to insulate and increase the velocity of the signals relayed by nerve cells. Gaps between segments of myelin, called nodes of Ranvier, also work to amplify these signals.

Myelin layers are currently considered static once formed, maintaining the same mature structure throughout a person’s life. However, this study found the mature myelin sheath is dynamic, and can become thinner or thicker through the action of astrocytes working to regulate transmission speed.

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“Scientists used to think that myelin could not be thinned except when destroyed in demyelinating diseases, such as multiple sclerosis,” R. Douglas Fields, PhD, a section chief at the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the study’s senior author of the study, said in as news release.

“Our study suggests that under normal conditions, the myelin sheath and structure of the nodes of Ranvier are dynamic, even in adults,” Fields added.

Nerve impulses must travel and arrive at relay points extremely quickly for effective connection and communication between brain regions. The speed of these impulses “is critical for optimal neural circuit function, but it is unclear how the appropriate conduction velocity is established,” the researchers wrote.

Their goal was “to understand how myelin, and the cells that regulate it, help synchronize signals that come from different areas of the brain,” said Dipankar Dutta, PhD, an NICHD researcher and lead author of the study.

Focusing on perinodal astrocytes, which connect to nodes of Ranvier, and experimenting with mice and rats, the researchers saw that astrocytes are able to prevent myelin loss — thinning — by releasing molecules that inhibit an enzyme called thrombin.

Thrombin cuts adhesion molecules that connect myelin to nerve fibers, so as to trigger the detachment of myelin layers from an axon. This enzyme also plays a key role in blood coagulation, promoting the formation and cross-linking of fibrin to form a clot.

When researchers blocked the ability of perinodal astrocytes to inhibit thrombin, myelin sheaths thinned and nodes of Ranvier widened. These alterations significantly diminished the velocity of nerve impulse transmission, enough to impair reflexes in the mice analyzed.

The findings suggest that astrocytes, by regulating the thickness of the myelin sheath, also regulate the velocity of signal speed — so to have an important role in how the brain processes information.

Based on their findings, the researchers believe that medications — anticoagulants — able to inhibit thrombin may help to stabilize myelin around nerve fibers in people with myelin loss (demyelination), like MS patients.

A number of thrombin inhibitors are approved by the U.S. Food and Drug Administration (FDA) to prevent blot clots from forming and traveling to blood vessels — conditions known as arterial and venous thrombosis. The research team is evaluating if these medications may be protective of myelin in a mouse model of MS.