Basic fibroblast growth factor down‐regulates myelin basic protein gene expression and alters myelin compaction of mature oligodendrocytes in vitro

Abstract

The effects of basic fibroblast growth factor (bFGF) on myelin basic protein (MBP) gene expression and myelin-like membrane formation were investigated in oligodendrocyte cultures containing mainly mature oligodendrocytes expressing MBP. These cultures were obtained by selective detachment of the cells of the oligodendrocyte lineage from 40-day-old mixed cultures derived from newborn rat brain. They were further purified by a 3-day pretreatment with cytosine arabinoside (ARA-C) in order to kill cycling cells. After withdrawal of ARA-C, daily treatment of the cells with bFGF for 3 days induced a drastic decrease in MBP mRNA level compared to control cultures treated only with ARA-C. Moreover, the percentage of oligodendrocytes labelled with anti-MBP antibodies decreased by 50%, as well as that of oligodendrocytes expressing myelin oligodendrocyte glycoprotein (MOG), whereas proteolipid protein (PLP) immunolabelled cells were less affected. At the ultrastructural level, myelin-like membranes were still abundant in the ARA-C- and bFGF-treated cultures, but they were conspicuously uncompacted compared to cultures only pretreated with ARA-C. These results bring the first evidence that bFGF is able to down-regulate myelin protein gene expression in mature oligodendrocytes and to alter myelin structure. They imply that if bFGF is secreted after a demyelinating lesion of the central nervous system (CNS), this plasticity of mature oligodendrocytes will allow final remyelination of axons to complete only after this factor has returned to low levels.