Journal News

How is myelin made?

Understanding the protective coating on neurons may inform future therapies
Nuala Del Piccolo
April 14, 2020

Myelin is the protective lipid sheath wrapped around a nerve. It functions as an insulator, akin to the protective coating on a wire, speeding up electrical transmission of signals along a neuron. Myelin also plays a role in maintaining the health of neurons. Myelin function is dysregulated in many neurological disorders, including multiple sclerosis.

Jennifer Siow
This artist’s rendition, created by the first author's daughter, shows neurons with (right) and without (left) a myelin sheath. The neuron with a myelin sheath functions at full capacity, while a neuron without myelin is unhealthy. Oligodendrocytes are depicted in red.

Oligodendrocytes are the myelin-producing cells of the central nervous system. The myelin sheath around a neuron is part of an oligodendrocyte’s plasma membrane, and a single oligodendrocyte can myelinate as many as 50 neurons. During myelination, an oligodendrocyte stretches out tubes of membrane in search of a neuron. When it finds one, it sends the necessary building materials down the tubes and, still operating from a distance, assembles a myelin sheet around the neuron: Composition, number of wraps and total coverage all matter. A myelinated neuron that loses its coating cannot transmit electrical signals properly, leading to loss of muscle control and other neurological problems. 

The myelin sheath is mostly made of lipids, including sphingolipids, which are critical to myelin’s structure and function. The enzyme serine palymitoyltransferase, or SPT, produces the backbone of all sphingolipids, and the membrane-bound protein ORMDL monitors sphingolipid levels and regulates SPT activity. ORMDL’s activity must be precise: Too little sphingolipid production impedes myelination, and too much can be toxic. 

Binks Wattenberg, a professor of biochemistry and molecular biology at Virginia Commonwealth University, studies membrane biogenesis and now focuses on lipid biogenesis. “I am very curious about how the cell knows when to make sphingolipid and when to stop,” Wattenberg said. “I think ORMDL might be the key to answering that question.” 

Wattenberg’s next-door lab neighbor, Carmen Sato–Bigbee, a professor in the same department, studies myelination, with a focus on oligodendrocytes. The two joined forces to study the role of sphingolipid biosynthesis in myelination in developing brains. They report their recent results in the Journal of Lipid Research

To uncover the dynamics of sphingolipid content and synthesis during myelination, Wattenberg and Sato–Bigbee’s team worked with newborn rat brains, because peak myelination occurs directly after birth. Only one in five cells in the brain is an oligodendrocyte, so the team isolated these myelin-producing cells for their experiments. 

The researchers found that a large portion of the sphingolipids present in oligodendrocytes during myelination have an atypically long backbone — an 18-carbon chain instead of a 16-carbon chain. “The 18-carbon chain backbone points to a change in lipid composition during myelination, which might explain the insulating properties of myelin,” Wattenberg said. “In future work, we want to look at the role of each type of sphingolipid in myelination.”

The study also found that SPT activity increases for the first few days of myelination and then begins to decrease. ORMDL activity is not measurable, but the team deduced that ORMDL isoform expression varies over time. These findings pave the way for future experiments. 

“The control of sphingolipid biosynthesis is key to myelination, and understanding how this process works will enable us to alter it in future treatments,” Wattenberg said. “Our pie-in-the-sky goal is to understand sphingolipid biosynthesis so well that we can reprogram oligodendrocytes and reverse demyelination in degenerative myelination diseases like MS.”

 

Nuala Del Piccolo

Nuala Del Piccolo is a postdoctoral scholar in the biomedical engineering department at the University of California, Davis. She earned her Ph.D. in materials science and engineering at Johns Hopkins University.

Join the ASBMB Today mailing list

Sign up to get updates on articles, interviews and events.

Latest in Science

Science highlights or most popular articles

From the journals: JLR
Journal News

From the journals: JLR

August 11, 2020

A hopping, scooting enzyme; the role of mycolic acid biosynthesis in TB; ceramide reduction to treat liver disease. Read about these recent papers in the Journal of Lipid Research.

Searching high and low for the origins of life
News

Searching high and low for the origins of life

August 09, 2020

Researchers think they’re getting warmer: They’ve created amino acids and primitive membranes by simulating conditions found at scalding vents on the ocean floor.

Why hydroxychloroquine and chloroquine don't block coronavirus infection of human lung cells
News

Why hydroxychloroquine and chloroquine don't block coronavirus infection of human lung cells

August 08, 2020

Scientists in Germany tested the malaria drugs on various cell types and found they can block coronavirus infection in kidney cells from the African green monkey but don’t inhibit the virus in human lung cells.

JLR’s new article format puts images at the forefront
Journal News

JLR’s new article format puts images at the forefront

August 04, 2020

“Images in Lipid Research” series aims to celebrate the images scientists create.

Psoriasis Awareness Month 2020
Health Observance

Psoriasis Awareness Month 2020

August 03, 2020

An estimated 125 million people worldwide are affected by psoriasis. Learn about the disease and recent research on it.

The color of COVID
News

The color of COVID

August 02, 2020

In a summer dominated by COVID-19 and protests against racial injustice, there are growing demands that drugmakers and investigators ensure that vaccine trials reflect the entire community.