BRAIN-DERIVED NEUROTROPHIC FACTOR MODULATES GAP-43 BUT NOT T-ALPHA-1 EXPRESSION IN INJURED RETINAL GANGLION-CELLS OF ADULT-RATS

The administration of neurotrophins affects neuronal survival and grow th, but less is known about their ability to modify the expression of growth associated genes following injury to CNS neurons, Here we chara cterize the effect of brain-derived neurotrophic factor (BDNF) on mRNA levels for T alpha 1 alpha-tubulin, and for GAP-43, two genes whose e xpression levels in retinal ganglion cells (RGC) tend to correlate wit h growth, We first determined that most adult rat RGCs can retrogradel y transport BDNF by injecting I-125-BDNF into RGC target sites in vivo . We then used quantitative in situ hybridization to characterize the effect of axotomy, or axotomy and BDNF administration on mRNA levels f or GAP-43 and T alpha 1. Axotomy alone resulted in a general decrease in T alpha 1 alpha-tubulin mRNA levels by 2 weeks, and elicited an inc rease in GAP-43 mRNA levels in an average of 30% of surviving RGCs, Th e intravitreal administration of a single dose of BDNF (5 Ecg) to axot omized RGCs on the day of injury did not affect T alpha 1 alpha-tubuli n mRNA levels, but was followed by a moderate (approximately 80%), and short-lasting enhancement of GAP-43 mRNA levels in most RGCs during t he first week after axotomy, No significant increase in GAP-43 mRNA le vels was observed when BDNF was injected into the uninjured eye, We co nclude that BDNF specifically enhances GAP-43 but not T alpha 1 mRNA l evels in injured RGCs, Because BDNF is known to stimulate branch lengt h of injured RGCs, we suggest that changes in the expression of GAP-43 , but not Toll tubulin, correlate with branching of injured neurons as opposed to long distance regrowth. (C) 1997 Wiley-Liss, Inc.