oligodendrocyte

Oligodendrocytes, also known as oligodendroglia, belong to a class of cells in the central nervous system known as glial cells. Oligodendrocytes are responsible for producing a fatty protein, called myelin, which insulates axons, the long extensions of nerve cells (neurons). Myelinated axons transmit nerve signals much faster than unmyelinated ones. Each oligodendrocyte can supply myelin for several axons and each axon can be supplied by several oligodendrocytes. Oligodendrocytes wrap the myelin around the axons in thin sheets like rolled up paper. Schwann cells, another kind of glial cell, makes a slightly different kind of myelin in the peripheral nervous system.

When parts of the myelin sheath is lost, oligodendrocytes attempt to replace it. However, in multiple sclerosis, it appears that the oligodendrocytes, themselves, are often destroyed thus compromising the repair process. There are several different types of multiple sclerosis lesions and the effect on and behaviour of oligodendrocytes seems to vary between these types:

• In acute MS lesions, typical of very aggressive disease courses, oligodendrocytes are found in large numbers and there is evidence of abortive remyelination - probably the new myelin is being destroyed faster than the oligodendrocytes can lay it down.

• Chronic active MS lesions appear to spread outwards from the centre with all the activity at the well defined margins. The lesions have scarred centres that are devoid of oligodendrocytes and have minimal immune system activity. The reduced numbers of axons are shrunken and heavily demyelinated. The destruction happens at the inflammed margins where there are many macrophages, a type of immune system cell. There are many oligodendrocytes and evidence of some remyelination.

• Chronic silent MS lesions seem to be largely immunologically inactive. Again they are sharply demarcated from the surrounding normal white matter and contain a reduced number of demyelinated axons and no oligodendrocytes at the centre. At the margin, there is a thin band of remyelination and many oligodendrocytes. Some silent lesions show extensive remyelination.

What accounts for the destruction of oligodendrocytes in MS is not clear, though it would appear from recent work that oligodendrocytes are not immunologically inert and that, apoptosis - "programmed cell death" – is at least partially responsible. Aptosis is a process whereby cells "commit suicide" in response to receiving signalling molecules, called cytokines, from other cells. The cytokines Tumour Necrosis Factor-alpha (TNF-alpha), LymphoToxin-alpha and -beta (LT-a and LT-b) and interferon-gamma (INF-g) all appear to be involved in the aptosis of oligodendrocytes in multiple sclerosis.

Some research work is looking at how to replace the lost oligodendrocytes and thereby the lost myelin. Oligodendrocytes mature from stem cells called O-2A progenitor cells which can be purified and grown in large numbers in cell cultures outside the human body. In the developing central nervous system, O2-A cells freely migrate to where oligodendrocytes are needed and researchers are looking at ways to use these cells to heal the damage done at the site of MS lesions.

Oligodendrocyte links:

Oligodendrocytes

Oligodendrocyte (only works in Internet Explorer)

Multiple Sclerosis: Immunologic interactions with the oligodendrocyte

Oligodendrocyte precursor (O-2A progenitor cell) migration

Remyelination in MS

Myelin from an oligodendrocyte wrapping around spinal cord axon

The effect of neuregulin-2 on myelinating cell precursor proliferation