Toxic and trophic effects of glial-derived factors on neuronal cultures

To test the hypothesis that glial-derived factors exert differential effects on neurons in developing and aged brain, we treated NB2a/d1 neuroblastoma cells with conditioned medium (CM) obtained from C6 glioma cells. Undifferentiated NB2a/d1 cells rapidly (< 4 h) elaborated neurites in response to CM. Cells previously differentiated by 14 days treatment with 1 mM dbcAMP, which induces outgrowth of axonal neurites, exhibited no obvious effects when exposed to CM. By contrast, CM was toxic to cells that were treated with 1 mM dbcAMP for 7 days followed by 7 days in which dbcAMP had been reduced to 0.1 mM or withdrawn. These results highlight the potential of glial-derived factors to exert trophic and toxic effects depending upon neuronal differentiation state.