Myelin-Producing Cells Behave Differently Depending on Location

Researchers at Rutgers University have discovered that specialized cells called oligodendrocytes, which produce the myelin sheaths that protect nerve cells, have different metabolic processes depending on whether they are located in the brain or spinal cord. They also characterized how these differences affect biosynthesis of key myelin component cholesterol. These insights could contribute to development of treatments that prevent or repair nerve damage in neurodegenerative diseases like multiple sclerosis.

“[Brain and spinal oligodendrocytes] look identical under a microscope, so everyone assumed they were the same,” says Teresa Wood, a Distinguished Professor and the Rena Warshow Endowed Chair in Multiple Sclerosis, who led the Rutgers team. “We drilled down to see what the cells are doing from a biochemical and molecular biological perspective. And we found they are definitely different.”

Brain imaging in people with multiple sclerosis often shows lesions—abnormalities in the myelin coating—in the brain or spinal cord. In these cases, the myelin has disappeared and oligodendrocytes have died off. A loss of myelin leads to impairments in everything from vision to muscle control. Myelin loss is also seen in brain images of patients with Alzheimer’s disease, autism and schizophrenia, but the causation is not well understood, Wood said.

One hope for treatment lies in locating immature cells positioned throughout the central nervous system that will mature into oligodendrocytes to produce myelin and repair the lesions. However, better understanding of the characteristics of oligodendrocytes is required for this to be effective, Wood says.

While evaluating the differences between brain and spinal oligodendrocytes, the team made three key discoveries. First, they found that cholesterol, a building block of myelin, is produced by oligodendrocytes in the spinal cord at a greater efficiency and volume than oligodendrocytes in the brain. Understanding how and where a building block of myelin is produced could assist researchers looking for ways to thwart myelin destruction or to promote myelin repair in certain areas.

The group also found that a cell protein known as mTOR, or Mechanistic Target Of Rapamycin, is necessary for the production of cholesterol in oligodendrocytes. By recognizing this protein, researchers may be able to target it to enhance cholesterol and myelin production. Thirdly, they found that mTOR is also critical for maintaining the already-formed myelin structures in the central nervous system.

The findings were published recently in the journal Cell Reports.