[Development and regeneration of oligodendrocytes: therapeutic perspectives in demyelinating diseases]

The function of the central nervous system (CNS) is in great part depending on glial cells as, for instance, radial glial cells give rise to cortical neurons, and oligodendrocytes synthesize an immense specialized membrane that enwraps axons to make myelin internodes. Myelin allows fast saltatory conduction of action potentials along myelinated nerve tracts and assures the survival of axons. Oligodendrocytes precursors (OP) emerge during development, first in the spinal cord and later in the telencephalon from multipotential neural precursors in germinative zones around the cerebral ventricles. Morphogens and specific growth factors stimulate the growth, migration and survival of OPs toward axons, culminating in myelination. Such precursors can be isolated from human brain and persist in the adult CNS, allowing some degree of remyelination in the course of a demyelinating disease caused by an infectious agent or inflammation such as multiple sclerosis (MS). These remyelinating cells can recapitulate some molecular events of myelination while new OPs are generated by neural stem cells in the subventricular zones and niches. This natural repair process often decreases with time in man, raising questions about the appropriateness of rodent animal models where remyelination is robust. The challenge today in MS is to develop a pharmacology of myelin repair by endogenous precursors which, if successful, might be more likely to result in clinical benefits than transplantation of myelin-forming cells, shown to be so efficient in rodent models.