Regulation of Oligodendrocyte Development and CNS Myelination by IGF-I: Prospects for Disease Therapy

Abstract

Myelin is an innovation that arose relatively recently during evolution, being found only in vertebrates and not in lower taxa. In axons ensheathed by myelin, which forms a series of insulating segments or “internodes” separated by uninsulated nodes of Ranvier, action potentials are conducted in saltatory fashion, jumping from one node of Ranvier to the next without depolarizing the axonal membrane covered by the intervening myelin. As a result, thin myelinated axons can conduct action potentials at the same velocity as much thicker unmyelinated axons, allowing considerable savings in space without sacrificing performance. Moreover, because membrane depolarization and ion flux occur only at the nodes of Ranvier, myelin reduces the energy cost of conduction by a factor of 100 or more. Without the miniaturization and energy efficiency enabled by myelination, the highly complex nervous systems of vertebrates would not be possible. The importance of myelin to neural function is strikingly illustrated by the devastating consequences of demyelination in multiple sclerosis (MS). However, in spite of myelin’s fundamental role in nervous system function and its involvement in MS and other human diseases, relatively little is known about the regulation of myelin production by the myelin-forming cells of the central and peripheral nervous systems (CNS and PNS), oligodendrocytes and Schwann cells, respectively. Clarification of these processes would give us a better fundamental understanding of nervous system development and function, and would likely yield information useful in designing therapies to promote remyelination in MS and other myelin diseases.