CYCLIC-AMP DECREASES THE EXPRESSION OF A NEURONAL MARKER (GAD(67)) AND INCREASES THE EXPRESSION OF AN ASTROGLIAL MARKER (GFAP) IN C6 CELLS

C6 cells express proteins and mRNAs that are characteristic of both gl ia and neurons. Agents that increase intracellular levels of cyclic AM P (cAMP) decrease the enzymatic activity of glutamate decarboxylase (G AD), a neuronal marker, and the mRNA levels for one of the two GAD iso enzymes, GAD(67). This reduction is accompanied by increased levels of glial fibrillary acidic protein (GFAP) mRNA, an astrocyte marker. Tra nsient transfection assays, in which a 2-kb upstream regulatory region of the human GFAP gene was linked to a reporter gene, indicate that a t least some of the cAMP-mediated increase of GFAP mRNA levels is due to increased transcription. Increases in intracellular cAMP appear to induce differentiation of C6 cells toward a more mature astrocyte phen otype.