BASIC FIBROBLAST GROWTH-FACTOR DOWN-REGULATES MYELIN BASIC-PROTEIN GENE-EXPRESSION AND ALTERS MYELIN COMPACTION OF MATURE OLIGODENDROCYTES IN-VITRO

The effects of basic fibroblast growth factor (bFGF) on myelin basic p rotein (MBP) gene expression and myelin-like membrane formation were i nvestigated in oligodendrocyte cultures containing mainly mature oligo dendrocytes 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 puri fied by a 3-day pretreatment with cytosine arabinoside (ARA-C) in orde r 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 myel in oligodendrocyte glycoprotein (MOG), whereas proteolipid protein (PL P) immunolabelled cells were less affected. At the ultrastructural lev el, myelin-like membranes were still abundant in the ARA-C- and bFGF-t reated cultures, but they were conspicuously uncompacted compared to c ultures only pretreated with ARA-C. These results bring the first evid ence 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 n ervous system (CNS), this plasticity of mature oligodendrocytes will a llow final remyelination of axons to complete only after this factor h as returned to low levels. (C) Wiley-Liss, Inc..