TRANSCRIPTION FACTOR EXPRESSION IS INDUCED BY AXONAL STIMULATION AND GLUTAMATE IN THE GLIA OF THE DEVELOPING OPTIC-NERVE

Recent experiments have demonstrated that stimulation of the developin g optic nerve affects several glial cell characteristics, such as ioni c fluxes and cell proliferation. This investigation asked if transcrip tion factor expression may be another stimulation-dependent process in the glia of the developing optic nerve. In unstimulated optic nerves, an antibody to c-fos-related antigens demonstrated positive cell body staining at postnatal days (P) 2, 7, 14, and 60. This nuclear stainin g was most prominent at early postnatal ages, although young adult (P6 0) optic nerves showed occasional positive cells. To demonstrate the i nducibility of transcription factor antigens, optic nerves from P7 ani mals received intermittent 15-20 Hz electrical stimulation for 5-15 mi n. Two hours after this stimulation, an increased number of immunoreac tive cells for c-fos-related antigens, c-jun, and NGFI-A was demonstra ted. Additionally, optic nerves were exposed for 5-30 min to a solutio n of 300 muM glutamate, latter maintained in a glutamate-free solution for 2 h, and then quickly frozen. Glutamate-treated nerves showed an increased expression of c-fos-related antigens compared to control ner ves. No c-fos increase was seen in the absence of calcium. Expression of c-fos or NGFI-A occurred in cells that were S-100 positive, and mos t likely represented type 1 astrocytes. These studies indicate that de veloping (P7) optic nerves show a baseline expression of c-fos-related antigens, c-jun and NGFI-A. Stimulation through electrical nerve stim ulation or glutamate results in an increased expression of these trans cription factors.