Glial-released proteins: III. Influence on neuronal morphological differentiation.

In vitro model systems in neurobiology are available to detect and help characterize various intercellular development signals. The presence of such active substances in conditioned medium (CM) from rat C6 glioma cells (2BD clone) was examined using the pheochromocytoma-derived clonal cell lines PC12 and PCG2. Conditioned medium from C6 monolayers induces neurite outgrowth in PC12 cells and extensive alteration in PCG2 cell morphology by 24 h. This ability of CM was found (1) to remain after dialysis and lyophilization, (2) to be modulated by steroid treatment of C6 monolayers (PC12 cells only) and (3) to be distinct from the influence of NGF. Combinations of CM, nerve growth factor (NGF) and dibutyryl cyclic AMP when given together in pairs to PC12 or PCG2 cells revealed facilitation of neurite formation and cell morphology, respectively. These results suggest possible synergistic interaction between the three factors in the neuroglial regulation of neuronal morphological differentiation.