Contrasting effects of mitogenic growth factors on myelination in neuron-oligodendrocyte co-cultures

Mitogenic growth factors play an important role in the initial stages of oligodendrocyte development, but their roles in the process of myelination itself remain less well defined. In order to study directly the effects of different growth factors on myelination, we used a purified in vitro co-culture system with dorsal root ganglion neurons and oligodendrocytes. Extensive myelination had occurred in these cultures 14 days after oligodendrocyte precursors (OPCs) were added, with the relationship between neurite density and the percentage of oligodendrocytes forming myelin sheaths providing a robust and straightforward means of quantifying myelination. Addition of soluble neuregulin (Nrg1), a mitogen for oligodendroglial cells that also provides an axonal signal implicated in oligodendrocyte survival, increased myelination. Conversely, the OPC mitogens FGF-2 and PDGF inhibited myelination. The inhibitory effect of these mitogens was reversible, as inhibition of PDGF allowed myelination to proceed. Taken together, these data indicate that different mitogenic growth factors can regulate myelination by oligodendrocytes in addition to their well-described effects on earlier stages of oligodendroglial development. Moreover, the results highlight important differences between the growth factors.