Enzyme ensures thick insulation

March 8, 2018 by Pe­ter Rüegg, ETH Zurich
Schwann cells build up the blue insulation layer of a nerve fibre. If these cells lack a certain enzyme, the isolation is inadequate. Credit: Alfred Pasieka / Science Photo Library / Keystone

ETH researchers have revealed that Schwann cells in the peripheral nervous system largely produce their own fatty acids in order to create electrical insulation for nerve fibres. This process relies on an enzyme whose absence leads to defective insulation and impaired motor function.

Axons, the long projections of which form the nerves of our peripheral nervous system, are like electrical cables: they have thick electrical insulation so that they can quickly relay stimuli from the body and signals from the brain to a toe, for example.

This insulation, called myelin, is made up of numerous layers of cellular membranes – seen in cross section, an axon insulated in this way resembles the rings of a tree. These myelin sheaths have constrictions (or nodes) at regular intervals, and nerve impulses jump from one node to the next in order to propagate quickly.

Defective insulation

In some neurodegenerative diseases, the myelin sheaths of axons in the peripheral nervous system degrade, meaning they can no longer relay signals and commands efficiently. One example of these diseases is Charcot-Marie-Tooth disease (CMT), which is an inherited condition. Over time, the breakdown of the insulation leads to degeneration of the nerves and ultimately also of the muscles that are cut off from as a result. As the disease progresses, patients lose the ability to control their motor functions and can barely walk properly, as well as suffering from pain.

Building up the axons' insulation is the responsibility of the surrounding Schwann . These use large quantities of various fat molecules (lipids) in a short time, mostly in the first years after birth, to encase axons in myelin. Until now, it was not known how they satisfied their huge need for lipids. Scientists debated if they obtained these molecules from food or produced them themselves.

Central enzyme for synthesis

Researchers at ETH Zurich, led by Laura Montani from the group of Ueli Suter at the Institute of Molecular Health Sciences, have now used a mouse model to demonstrate that the Schwann cells synthesise around half of the lipids needed for building up the insulation from scratch – that is, they produce them themselves. The cells obtain the other half of the lipids they need from food.

Like tree rings: layers of myelin coat a nerve fibre. Credit: wikimedia commons

Sitting inside the Schwann cells, an enzyme known as fatty acid synthase (FASN) acts as a central "switch" in the process of synthesising lipids. The team found that this enzyme is essential for the correct composition of lipids in the insulating layers, for the cells to start myelination, and for the healthy growth of myelin layers. Via the produced, called , FASN also regulates an entire signal network that plays an important role in myelination.

Once this enzyme is missing, the cells can no longer produce critical lipids for the myelin layers. The Schwann cells then rely more heavily on obtaining dietary lipids from blood vessels that pass through . However, Schwann cells laying more far away from the bloodstream can neither synthesise their own lipids nor obtain them well from the blood and therefore cannot insulate the axons sufficiently – if at all.

In addition, the researcher and her colleagues from various universities, including the Universities of Graz (Austria), Washington-St. Louis (USA) and Zurich, found that even a high-fat diet failed to reverse the process in mice that lacked the enzyme FASN: the axons' insulation remained defective. This shows that intrinsic lipid production by Schwann cells is essential for the formation of in the nerves.

Montani and her colleagues conducted their experiments using animals with a specific mutation that meant they lacked the enzyme FASN. Her study compared the myelination of these mice with that of mice in which FASN did occur. The study examined animals in their "childhood", from birth onwards, as this is the critical stage of life in which axons receive their myelin insulation. After adolescence, myelination is more or less complete. The will still be thickened if need be, but the phase of rapid build-up is over.

Connection with rare neurological diseases?

It remains unclear what implications the results have for different diseases. Montani is now studying if the is also crucial for the cells which myelinate the brain during postnatal development and if it plays a role in repairing myelin after a lesion, as the ones present in multiple sclerosis patients.

A large number of rare childhood diseases stem from mutations in genes that play an essential role in . Little research exists into these diseases, as they occur very rarely. The patients typically die at a very young age due to severe degeneration of the nervous system.

Montani suspects that the breakdown of neurons could be caused by reduced synthesis of lipids in the myelinating cells of the nervous system, among other factors. "Knowing how reduced synthesis affects myelination during development is an important step towards gaining a better understanding of how these kinds of diseases progress," she says.

Moreover, although very few people suffer from each of these disorders, she says rare disorders as a whole are one of today's biggest causes of death in babies and infants in the industrialised nations. They are responsible for around a third of deaths in the first year of life. Montani therefore wants to continue her research in this direction in the future. As the fruit of six years of hard work, her project is now complete and will provide the foundation for this future research.

Explore further: Experimental therapy restores nerve insulation damaged by disease

More information: Laura Montani et al. De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination, The Journal of Cell Biology (2018). DOI: 10.1083/jcb.201706010

Related Stories

Experimental therapy restores nerve insulation damaged by disease

February 12, 2018
When the body attacks its own healthy tissues in an autoimmune disease, peripheral nerve damage handicaps people and causes persistent neuropathic pain when insulation on healing nerves doesn't fully regenerate.

Glial cells assist in the repair of injured nerves

January 28, 2013
When a nerve is damaged, glial cells produce the protein neuregulin1 and thereby promote the regeneration of nerve tissue.

The key to treating multiple sclerosis could be inside sufferers' own bodies

February 28, 2018
Fat often gets a bad press, but if it didn't coat the cables that connect our neurons, we'd be in a lot of trouble. Sufferers of multiple sclerosis and a host of other nervous system diseases have first-hand experience of ...

Evidence for myelin sheath remodeling revealed by in vivo imaging

February 15, 2018
Nerve fibers are surrounded by a myelin sheath. Scientists at the Technical University of Munich (TUM) have now made the first-ever "live" observations of how this protective layer is formed. The team discovered that the ...

Recommended for you

Common painkiller not effective for chronic pain after traumatic nerve injury

September 24, 2018
A new study out today in the Journal of Neurology finds that pregabalin is not effective in controlling the chronic pain that sometimes develops following traumatic nerve injury. The results of the international study, which ...

Implant helps paralysed man walk again

September 24, 2018
Five years after he was paralysed in a snowmobile accident, a man in the US has learned to walk again aided by an electrical implant, in a potential breakthrough for spinal injury sufferers.

Study of protein 'trafficker' provides insight into autism and other brain disorders

September 22, 2018
In the brain, as in business, connections are everything. To maintain cellular associates, the outer surface of a neuron, its membrane, must express particular proteins—proverbial hands that reach out and greet nearby cells. ...

Breast milk may be best for premature babies' brain development

September 21, 2018
Babies born before their due date show better brain development when fed breast milk rather than formula, a study has found.

White matter repair and traumatic brain injury

September 20, 2018
Traumatic brain injury (TBI) is a leading cause of death and disability in the U.S., contributing to about 30 percent of all injury deaths, according to the CDC. TBI causes damage to both white and gray matter in the brain, ...

'Gut sense' is hardwired, not hormonal

September 20, 2018
If you've ever felt nauseous before an important presentation, or foggy after a big meal, then you know the power of the gut-brain connection.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.