Re-entry into the cell cycle is required for bFGF-induced oligodendroglial dedifferentiation and survival.
Remyelination in the CNS following demyelinating disease may be accomplished by surviving mature oligodendrocytes that dedifferentiate, proliferate, migrate, and finally regenerate myelin. We previously reported that basic fibroblast growth factor (bFGF) induces oligodendrocytes in primary mixed glial cultures to dedifferentiate and synthesize DNA (Grinspan et al.: J Neurosci Res 36:672-680, 1993). We now show that this effect is direct and not mediated through the effects of bFGF on other cell types, because we were able to demonstrate similar changes in oligodendrocyte phenotype in enriched oligodendrocyte cultures prepared by immunopanning. The bFGF-induced reversion to the precursor stage of the oligodendroglial lineage can be blocked by agents that inhibit entry to the cell cycle; thus oligodendroglial dedifferentiation is dependent on proliferation. We also report that 2 days of bFGF treatment inhibits oligodendroglial apoptosis. However, when oligodendroglia are prevented from entering the cell cycle in the presence of bFGF, apoptotic cell death is increased. Thus, bFGF induces oligodendroglial dedifferentiation if oligodendroglial DNA synthesis can occur but causes oligodendroglial apoptosis when oligodendroglial DNA synthesis is prevented.
Grinspan
J B
JB
Department of Research Neurology, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Reeves
M F
MF
Coulaloglou
M J
MJ
Nathanson
D
D
Pleasure
D
D
D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000166:cytology; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004261:DNA Replication / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D009186:Myelin Sheath / Q000502:physiology; D009416:Nerve Regeneration; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D013936:Thymidine / Q000494:pharmacology
D016222:Fibroblast Growth Factor 2; D016590:Aphidicolin; D013936:Thymidine