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 developing optic nerve affects several glial cell characteristics, such as ionic fluxes and cell proliferation. This investigation asked if transcription 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 staining was most prominent at early postnatal ages, although young adult (P60) optic nerves showed occasional positive cells. To demonstrate the inducibility of transcription factor antigens, optic nerves from P7 animals received intermittent 15-20 Hz electrical stimulation for 5-15 min. Two hours after this stimulation, an increased number of immunoreactive cells for c-fos-related antigens, c-jun, and NGFI-A was demonstrated. Additionally, optic nerves were exposed for 5-30 min to a solution 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 nerves. 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 most likely represented type 1 astrocytes. These studies indicate that developing (P7) optic nerves show a baseline expression of c-fos-related antigens, c-jun and NGFI-A. Stimulation through electrical nerve stimulation or glutamate results in an increased expression of these transcription factors.