The transplantation of fibroblasts, genetically modified to secrete neurotrophin-3 (NT-3) and/or brain-derived neurotrophic factor (BDNF), into spinal cord-injured rats increases the production of new oligodendrocytes and myelination (McTigue et al. [1998] J. Neurosci. 18:5354-5365). This experiment did not fully resolve whether the effect was exerted on oligodendrocyte precursors or on oligodendrocytes, or whether there was stimulation of both proliferation and differentiation of the oligodendrocyte lineage cells. To clarify the effects of NT-3 and BDNF, adult rat spinal cord was dissociated to produce cultures in which both oligodendrocyte precursors (O1(-)O4(+)) and oligodendrocytes (O1(+)) were present. Thymidine labeling of cells was determined in the presence and absence of added NT-3 and/or BDNF. In addition, the effect of these neurotrophins on myelination was determined by treating purified adult O1(+) oligodendrocyte/embryonic dorsal root ganglion (DRG) neuron cocultures with neurotrophins, only during the myelination period. O1(+) oligodendrocyte proliferation was not stimulated by NT-3 or BDNF; however, the proliferation of O1(-)O4(+) cells was increased in NT-3-treated cultures to a labeling index (LI: 24 hr) of 15-20%. This effect was observed at 5 but not at 10 days in vitro. In comparison, basic fibroblast growth factor (bFGF) induced the proliferation of both O1(+) oligodendrocytes (LI approximately 60%) and O1(-)O4(+) cells (LI approximately 75%). The amount of myelin formed in purified O1(+) oligodendrocyte/DRG neuron cocultures was significantly increased in NT-3-treated cultures compared to untreated cultures. These results indicate that NT-3 is weakly but transiently mitogenic for adult-derived oligodendrocyte precursors and support the suggestion that NT-3 promotes the maturation of O1(+) oligodendrocytes into myelin-forming cells.
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