The cellular and molecular events of central nervous system remyelination

Abstract

Central nervous system (CNS)* regeneration is a subject of great interest, particularly in diseases causing a dramatic loss of neurons. However, some CNS diseases do not affect neurons but damage other cells, such as the myelin-forming cells--called oligodendrocytes--which are also crucial to the harmonious function of the nervous system. Diseases in which oligodendrocytes and myelin are attacked can cause devastating neurological dysfunction which is sometimes followed by recovery and myelin repair or remyelination. The question of the regeneration potential of oligodendrocytes in experimental and human demyelinating diseases such as multiple sclerosis has been debated for a long time. Present evidence suggests that oligodendrocyte precursor cells persist in the adult CNS and that oligodendrocyte regeneration can occur but may be limited by ongoing disease processes. Here we will briefly review recent advances which have broadened our understanding of the cellular and molecular events of CNS remyelination.

From Neural Stem Cells to Myelinating Oligodendrocytes

“…Yet, in most vertebrates, there is evidence that remyelination is an efficient repair mechanism in the CNS (reviewed by DuboisDalcq and Armstrong, 1990). This suggests the existence of a pool of precursor cells in the adult CNS.…”

Uptake and metabolism of fluorescent ceramide analogs by rat oligodendrocytes in culture

“…Oligodendrocytes, a type of macroglia, are the cells that synthesize, maintain j1,2] and after trauma regenerate [3] sheaths of myelin membrane around axons in the central nervous system. It has been estimated that during the period of active nlyelination -in the rat during its third postnatal week -an oligodendrocyte may synthesize and assemble as much as three times its own weight in myelin per day [4].…”

Transplantation of an oligodendrocyte cell line leading to extensive myelination.

“…4-7). As myelin facilitates rapid impulse conduction along most nerve tracts, the lack or loss of myelin can result in important neurological dysfunction (8,9).Although the development of the oligodendrocyte lineage has been studied extensively in vitro (4-7), the molecular mechanisms controlling the growth and migration of oligodendrocyte progenitors (OPs) in vivo, the recognition of axons, the coordinate synthesis of multiple myelin internodes, the regulation of myelin protein genes, and the death of superfluous oligodendrocytes are largely unknown. An understanding of these molecular mechanisms could be approached by using a growth-factor-dependent cell line in which gene transfer or targeting could be performed and tested in a transplantation paradigm.…”

“…4-7). As myelin facilitates rapid impulse conduction along most nerve tracts, the lack or loss of myelin can result in important neurological dysfunction (8,9).…”