Morphological changes and neural cell adhesion molecule expression in mouse cerebrum primary cultures following long-term exposure to phorbol ester.

The effect of phorbol 12-myristate 13-acetate (PMA) on development of brain cells in culture was investigated. Chronic treatment of brain cells from fetal ICR mouse with PMA resulted in a time-dependent loss of specific [3H]phorbol 12,13-dibutyrate binding, generally called 'down-regulation'. In contrast to control culture, neurons cultured in PMA (162 nM)-containing medium exhibited aggregation and neurite fasciculation, and then the neural cell adhesion molecule (N-CAM) was expressed selectively on neurons. Also, the number of astrocytes, which were positively stained with anti-glial fibrillary acidic protein antibody, decreased by treatment with PMA. These results suggest that the normal development of cultured brain cells is interrupted by PMA treatment, which may involve protein kinase C (PKC) in the differentiation of neural cells and cell-cell (neuron-neuron, neuron-astrocyte etc.) interaction as PKC is believed to be a receptor for PMA and is down-regulated by chronic treatment with PMA.