Oligodendrocyte precursor cells become heterogeneous with age: different functional cell states?

Myelin is essential for normal brain function, as it confers fast information transmission and trophic support for axons. The importance of myelin becomes evident in diseases where myelin is lost or damaged, as it leads to both mental and physical disability. Oligodendrocyte progenitor cells (OPCs), which remain in the adult CNS respond to the demyelinating injury by migrating to the lesion site where they differentiate into new myelinating oligodendrocytes to restore the lost myelin sheaths and thus neuronal function. But, this regeneration process often fails, notably in MS, leaving axons vulnerable to atrophy. Failure of remyelination is primarily due to a failure of OPC differentiation rather than a depletion of OPCs. To promote endogenous myelin repair it is essential to understand the mechanism that can regulate myelin as well as remyelination.

Neurotransmitters, growth factors and electrical activity influence OPCs in normal development and perhaps in disease. We, and others, have shown, that OPCs receive synaptic input from axons in the white matter and both OPCs and mature oligodendrocytes respond to glutamate via AMPA and NMDA receptors. Given that the glutamate receptors on OPCs are ideally situated to sense neuronal activity they may signal to them to initiate myelination.  However, not all OPCs express the same electrophysiological properties and, thus does this heterogeneity have a functional significance as OPCs will decipher neuronal activity in different way or is it solely a transitional stage prior to differentiation. This talk will review our recent findings demonstrating the heterogeneity of OPCs and address the question whether OPC heterogeneity rather reflects different functional states.