Myelination

Abstract

Myelination is the process of generating myelin by Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes (OL) in the central nervous system (CNS). Developmental myelination is regulated by a close coordination between OL development and axonal activity. At late embryonic to early fetal period, newly committed OPCs from neural stem cells (NSCs) proliferate rapidly to expand their population and then migrate extensively to target areas, where they differentiate into mature OLs in a stepwise manner. At mid-gestation, some differentiated mature OLs start to myelinate larger caliber axons in the spinal cord. Later, myelination extends to the hindbrain, midbrain, basal forebrain, and eventually the cerebral cortex. Myelination extends into most of the postnatal life. Myelination is regulated by both intrinsic and extrinsic factors, including axonal surface molecules and electrical activity. The basic functions of myelin, as soon understood at the time of its discovery a century ago, are to increase the conduction speed of action potentials and maintain axonal integrity. Research in the past few decades has revealed that myelin and OLs are critically involved in maintaining axonal health through metabolic and trophic support. Moreover, new myelin sheaths are continuously added to axons by existing adult OPCs, while the thickness of the myelin sheath, the length of internodes, and the size of the nodes of Ranvier can be modified by a variety of factors, including experiences, stressors, and certain medications. Thus, myelin plasticity plays critical roles in high-order brain functions such as fine motor control, memory formation, and cognition. Because myelin sheaths are vital to the health of axons and normal connectivity between brain regions, dysregulation in myelination during development or disruption of myelin sheaths in adulthood can lead to devastating neurological consequences and participate in the expression of psychiatric disorders.