Transient exposure to FGF2 enhances myelination in embryonic brain cell cocultures

Abstract

The amount of myelination in vivo and in vitro depends on the number of oligodendrocyte progenitors, their differentiation, and on the neuron function. It has been shown that continuous administration of FGF2, a mitotic and neuroprotective factor, allows oligodendrocyte progenitors to proliferate, but prevents them from differentiating and myelinating. This study was designed to test the effect of transient exposure to FGF2 on myelination in an oligodendrocyte/neuron coculture system. At 2 days in vitro, cultures were treated with a single dose of 20 ng/ml FGF2. Cell proliferation was determined by BrdU uptake. The number of cells of the oligodendrocyte lineage was determined by immunocytology of 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase). The maturation of oligodendrocytes and myelination was followed by immunocytological analysis of MBP (myelin basic protein). Electron microscopy was used to study the ultrastructure of myelin. BrdU uptake procedure showed an increase in cell proliferation in FGF2-treated cultures after 48 h of treatment. At 15–18 days in vitro, CNPase + and MBP + cells were much more abundant in cultures treated with FGF2 than in control cultures. We observed differentiation and maturation of oligodendrocytes and a higher degree of myelination in FGF2-treated cultures compared to controls. Electron microscopy showed the presence of myelin structures in FGF2-treated cultures that did not differ morphologically from those observed in control cultures. Transient exposure of cultured brain cells to FGF2 increased myelination in vitro. Administration of FGF2 over a short period might thus enhance remyelination in demyelinating diseases in vivo.