Myelin: A History, Function, and Potential
Written by Editor   
Tuesday, November 17, 2015 08:34 AM

Myelin is probably the hottest topic in multiple sclerosis research at the moment, but there was a time when the word was generally used to refer to any squishy white substance in the body.

Indeed, myelin has its roots in the Greek word for bone marrow, and it was at one point in history used to refer to this substance, along with others like it in the body.

So when exactly did myelin become solely the white fibrous material that insulates nerves in order to better conduct electrical signals?  A book on the history of glial cells -- non-neuronal cells that support the nervous system and include astrocytes and oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system involves two chapters on oligodendroctyes and one on myelin, all of which involved extensive research to find original publications in various European languages.

The author said it was fascinating to peer inside early researchers' minds and see what they thought the various cell types they were observing actually were.  Before the Second World War and the advent of electron microscopy, people had no preconception of what they were looking for, so they wrote these detailed descriptions. You can get a lot of information from these old papers.

It's well established that the first incidence of myelin observation was made in the 18th century by famous Dutch microscopist Antonie van Leeuwenhoek.  In a 1717 letter to the British Royal Society, Leeuwenhoek wrote, "Sometimes I observed a nervule ... to be completely surrounded by fatty parts ... extending here and there from the spinal marrow."

It wasn't until 1833 that Christian Ehrenberg in Berlin described myelinated nerves as cylindrical tubes with surrounding white matter, which he called medulla. Five years later, Robert Remak, also in Berlin, distinguished the surrounding "medulla" from the main part of the nerve, although he did not specifically call these distinct parts "axon" and "myelin."

Then in 1854, another Berliner, Rudolf Virchow, coined the word "myelin" from the Greek root, which translated to bone marrow.  He was the first to speculate that it acted as insulation, writing "the medullary sheath ... serves as an isolating mass, which confines the electricity within the nerve itself, and allows its discharge to take place only at the non-medullated extremities of the fibers."

But the word myelin was still used to describe many substances in the body that were whitish and of a similar texture: "without much structure and a bit like chewing gum -- slimy, with no real shape."

Louis Ranvier then reported in 1872 in Paris that the myelin sheath is discontinuous and displays periodic interruptions, which were, of course, named the nodes of Ranvier. But after that point, the function of myelin remained elusive and generated wild speculations.

Ralph Lillie suggested that it conducted electrical signals in 1925 -- almost 70 years after Virchow had suggested the same -- but that wasn't confirmed until 1949 by Huxley and Stampfli.

And finally, with wider use of electron microscopy after World War II, Betty Geren reported in Boston in 1954 that Schwann cells spiral myelin around nerves. Richard Bunge in 1962 showed that the oligodendrocyte was the primary source for deploying myelin around axons in the brain -- ending the school of thought that axons can secrete myelin on their own.

Myelin remodeling persists well into middle age in mice, although it generally remains relatively stable, researchers report.  Most myelin internodes remained stable over about 2 months in animals ages 11 to 14 months, but a small proportion of internodes were remodeled.  It seems that the number of oligodendrocytes is very constant, and in terms of myelin remodeling on the subcellular level, we do see changes in the dynamics of myelin internode number as well as changes in length.  But these account for a very small proportion, and the take-home message is that myelin is quite stable.

Oligodendrocytes generate myelin and spin it around axons in order to insulate electrical signals. Research has shown that most oligodendrocytes are generated in early life, but the development of myelin continues into adulthood. Demyelination is at the root of multiple sclerosis, and some efforts to treat progressive forms of the disease have focused on stimulating oligodendrocyte numbers and/or activity.

Newer studies have suggested that certain characteristics of myelin, such as the number and length of myelin internodes, the thickness of myelin sheaths, and myelin protein expression may be modified by sensory experience. They seem to show that oligodendrogenesis continues to a large extent in adult animals, but at a lower rate.  "We're interested in trying to understand whether oligogenesis is modulated in middle-aged animals, and if other aspects of oligogenesis that might be affected by sensory experience or life experience, such as modification of existing myelin, are affected,” authors report.  The work does suggest that while myelin turnover in the normal brain is very limited, "after a demyelinating injury or insult to the nervous system, the really amazing part is that the nervous system is still capable of repair even though under normal circumstances it's quite stable.

Remyelination has been a focal area in MS research, with the hope that restoring lost myelin could combat disease progression and possibly even reverse its course.  It was known that oligodendrocytes have the power to insulate axons with myelin, but it's not clear what goes wrong in that process in MS.