The Role of Oligodendrocytes in Remyelination

Post by Kayla Simanek

What's the science?

Oligodendrocytes are cells that produce myelin sheath, a fatty substance that insulates nerve fibers to ensure electrical signals are transmitted appropriately between neurons. Diseases like multiple sclerosis (MS) are characterized by demyelination (i.e. the loss of myelin sheath) causing nerve fiber breakdown. Remyelination is an innate repair function of the nervous system, effectively restoring function to previously demyelinated nerve fibers. In MS, natural remyelination becomes more deficient over time and ultimately results in disease progression. It was thought that myelin was repaired only by newly made oligodendrocytes, but recent evidence suggests that mature oligodendrocytes may participate in remyelination too. Understanding remyelination is critical for the therapeutic treatment of MS, because recruitment of all remyelinating cell types may be necessary to slow or reverse disease progression. This week in PNAS, Duncan and colleagues show that mature oligodendrocytes participate in remyelination within the central nervous system.

How did they do it?

The authors studied demyelinated models in both cats and Rhesus monkeys. Cats were fed an irradiated diet for 5-6 months and developed impaired coordination and weakness of the hind legs as a result of demyelination. The cats were then returned to a normal diet for recovery. The spinal cords of the cats were then collected either 2-3 months or 2 years after being returned to a normal diet. Spinal cord samples were analyzed using several microscopy techniques (light microscopy, transmission electron microscopy and scanning electron microscopy) to 1) characterize the structure of oligodendrocytes within the tissue and 2) determine the extent of demyelination and remyelination. The authors also studied archived material from Rhesus monkeys who had been fed a diet lacking vitamin B12 for three years. The spinal cords of monkeys were removed and examined via microscopy for oligodendrocyte structure and extent of remyelination.

What did they find?

The authors observed extensive demyelination within the ventral (front) and lateral (side) regions of the spinal cord of cats. Oligodendrocytes within these regions had extensions to both thick, mature myelin sheaths and thin, newly formed myelin. This indicates that these adult oligodendrocytes had not only survived the irradiated diet and maintained their preexisting myelin but were also starting to remyelinate nearby affected nerve fibers. The dorsal (back) region of the cats’ spinal cords had the most severe demyelination and primarily thin myelin sheath, and this region tended to lack surviving adult oligodendrocytes. A similar pattern was observed in spinal cords of Rhesus monkeys: Adult oligodendrocytes at the periphery of severe demyelination lesions were observed to have extensions to both pre-existing myelin sheaths and newly forming myelin on bare nerve fibers. Ultimately, this data suggests that mature oligodendrocytes do participate in central nervous system remyelination.

What's the impact?

This study found that mature oligodendrocytes actively remyelinate nerve fibers within the central nervous system. This is important for therapeutic treatment of demyelinating diseases like MS, because effective remyelination is important for the reversal of disease progression. The authors postulate that the severity of the demyelination might determine which cell type is involved in repair; new oligodendrocytes may be required for repair in regions of severe demyelination whereas adult oligodendrocytes were shown to remyelinate in more mildly affected areas.

Duncan et al. The adult oligodendrocyte can participate in remyelination. PNAS (2018). Access the original scientific publication here