Organization and structure in central-nerve myelin.

Degeneration of the myelin sheath in areas of the central nervous system is a characteristic feature of multiple sclerosis (Adams, 1977; Davison, 1978). The processes that cause this degradation of myelin during the course of the disease are not yet fully defined though the involvement of invading inflammatory cells is likely (Wisniewski, 1977). Any discussion on how the myelin sheath is attacked and broken down in situ during disease must be undertaken in the light of how the chemical constituents of the myelin membrane system are organized under normal conditions. An appreciation of the complex biosynthetic and metabolic interrelationships that exist between the myelin sheath and the myelin-synthesizing cell, and perhaps with the other cell types present in central nerve tissue, is also required. Research over the last decade especially has provided a general picture of the properties and structural organization of lipids and proteins in natural membranes (Singer, 1974) and it is now possible to relate the structural principles established for membranes in general to individual membrane systems. This exercise will be attempted for the myelin sheath of central-nerve tissue in this review. A much more comprehensive examination of myelin structure has been presented elsewhere (Morell, 1977; Rumsby & Crang, 1977). The compact myelin sheath of central-nerve tissue is characteristically revealed in electron micrographs as a multilamellar sequence of membrane (some 5-20 lamellae in number) that surrounds axons greater than about 1 pm in diameter (Fig. I). The length of an individual internodal myelin sheath is related linearly to the diameter of the axon and is often 1.5-2 orders of magnitude larger. We tend not to realize how long the lengths of internodal myelin are relative to the size of the myelin-forming cell; the average internodal length for mixed fibres in central-nerve tissue is about 250pm (Matthews & Duncan, 1971). The membrane of compact myelin is directly continuous with the plasma membrane of the oligodendrocyte, which is now considered to be the myelin-synthesizing and -sustaining cell in central-nerve tissue (Davison &Peters, 1970). There are now indications (e.g. Sabri & Davison, 1977) that neurons in the central nervous system do not participate in the synthesis of myelin components, as had once been suggested. Cytoplasm-filled processes extend from the body of each oligodendrocyte to form individual internodal myelin sheaths on closely adjacent axons (Fig. I) . In rat optic nerve each oligodendrocyte has between 30 and 50 processes (Peters & Vaughn, 1970). A single oligodendrocyte thus produces and sustains the membrane of many myelin sheaths. Norton & Poduslo (1973) have calculated that during the period of greatest membrane proliferation at myelination oligodendrocytes produce some 3 times their own weight of membrane every day. The synthetic capacity of these cells to produce the lipid and protein components of myelin is clearly prodigious. Now