The history of myelin

Abstract

Andreas Vesalius is attributed the discovery of white matter in the 16th century but van Leeuwenhoek is arguably the first to have observed myelinated fibers in 1717. A globular myelin theory followed, claiming all elements of the nervous system except for Fontana’s primitive cylinder with outer sheath in 1781. Remak’s axon revolution in 1836 relegated myelin to the unknown. Ehrenberg described nerve tubes with double borders in 1833, and Schwann with nuclei in 1839, but the medullary sheath acquired its name of myelin, coined by Virchow, only in 1854. Thanks to Schultze’s osmium specific staining in 1865, myelin designates the structure known today. The origin of myelin though was baffling. Only after Ranvier discovered a periodic segmentation, which came to us as nodes of Ranvier, did he venture suggesting in 1872 that the nerve internode was a fatty cell secreting myelin in cytoplasm. Ranvier’s hypothesis was met with high skepticism, because nobody could see the cytoplasm, and the term Schwann cell very slowly emerged into the vocabulary with von Lenhossék in 1895. When Cajal finally admitted the concept of Schwann cell internode in 1912, he still firmly believed myelin was secreted by the axon. Del Río-Hortega re-discovered oligodendrocytes in 1919 (after Robertson in 1899) and named them oligodendroglia in 1921, thereby antagonizing Cajal for discovering a second cell type in his invisible third element. Penfield had to come to del Río-Hortega’s rescue in 1924 for oligodendrocytes to be accepted. They jointly hypothesized myelin could be made by oligodendrocytes, considered the central equivalent of Schwann cells. Meanwhile myelin birefringence properties observed by Klebs in 1865 then Schmidt in 1924 confirmed its high fatty content, ascertained by biochemistry by Thudichum in 1884. The 20th century saw X-ray diffraction developed by Schmitt, who discovered in 1935 the crystal-like organization of this most peculiar structure, and devised the g-ratio concept in 1937. A revolution happened around the same time: saltatory conduction, the very reason for myelin existence, discovered by Tasaki in 1939 and confirmed by Huxley and Stämpfli in 1949. After the second world war, widely available electron microscopes allowed Geren to finally discover the origin of myelin in 1954, exactly a century after Virchow coined ‘myelin’ in 1854. Geren had the genial insight that the Schwann cell wraps around the axon and generates a spiral of compacted membrane–myelin. The central origin of myelin took a little longer due to the special configuration of oligodendrocyte distanced from the axon, but in 1962 the Bunges established the definitive proof that oligodendrocyte secretes myelin. The era of myelin biology had begun. In 1973 Norton devised a method to purify myelin which launched the modern molecular era.

Oligodendrogliopathy in neurodegenerative diseases with abnormal protein aggregates: The forgotten partner

“…These cells, called the "third element" turned out to be two different cell types after pioneering studies by Del Rio-Hortega (1921); one of these was microglia, the other oligodendroglia. The two cell types have different origins, morphology and functions; processes in some subtypes of oligodendroglial cells run in parallel to myelin thus suggesting a relationship between oligodendroglia and myelin (Penfield, 1924;Boullerne, 2016). Four different types were described by Pio del Rio-Hortega as detailed in a recent review (Perez-Cerda et al, 2015).…”

Oligodendrocytes: Morphology, functions and involvement in neurodegenerative diseases

“…The Scottish pathologist W. Ford Robertson first described cells that are now known as OLs. Initially, OLs were unnoticed until the silver staining method used by Pio del Rio Hortega in 1919 led to their discovery (6). Pio del Rio Hortega classified OLs according to the size and shape of their soma, the number of processes, their distribution, and their manner of interaction with axons with which they are associated.…”

Nongenetic Optical Methods for Measuring and Modulating Neuronal Response

“…In the 1980s, Ichiji Tasaki, who is also credited with helping discover the insulating properties of myelin sheaths 22,23 , pioneered a model of neuron firing where mechanical waves could propagate signals along the cell membrane 24 . Using light scattering across a fiber optic cable, Tasaki showed that when stimulated nerve fibers produced a barely perceptible swelling, resulting in mechanical deformations 25,26 .…”