APOPTOSIS OCCURS IN THE OLIGODENDROGLIAL LINEAGE, AND IS PREVENTED BY BASIC FIBROBLAST GROWTH-FACTOR

During the perinatal period, oligodendroglial precursor cells proliferate rapidly, then cease dividing and differentiate into oligodendroglia. Many of these newly formed oligodendroglia are destined to die. We now demonstrate that oligodendroglia generated in passaged cultures of rat forebrain oligodendroglial precursor cells after removal of basic fibroblast growth factor (basic FGF) from the medium often undergo internucleosomal DNA nicking and nuclear fragmentation, features characteristic of apoptosis. These alterations are rare in cultures maintained continuously in basic FGF. As in many other cellular lineages susceptible to apoptosis, these degenerative changes can be prevented by treatment with the endonuclease antagonist, aurintricarboxylic acid, or by inhibiting de novo RNA or protein synthesis. Supplementation of the basic FGF-free medium with insulin, insulin-like growth factor-1, platelet-derived growth factor, or ciliary neuronotrophic growth factor also diminishes DNA nicking. Both oligodendroglial differentiation and DNA nicking are induced in basic FGF-treated cultures by inhibiting DNA synthesis with aphidicholin or excess thymidine, thus suggesting a close linkage between the anti-apoptotic, antidifferentiation, and mitogenic effects of basic FGF on the oligodendroglial lineage. (C) 1995 Wiley-Liss, Inc.