Brain-derived neurotrophic factor modulates GAP-43 but not tα1 expression in injured retinal ganglion cells of adult rats
✍ Scribed by A.E. Fournier; J. Beer; C.O. Arregui; C. Essagian; A.J. Aguayo; L. McKerracher
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 969 KB
- Volume
- 47
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
The administration of neurotrophins affects neuronal survival and growth, but less is known about their ability to modify the expression of growth associated genes following injury to CNS neurons. Here we characterize the effect of brain-derived neurotrophic factor (BDNF) on mRNA levels for Ta1 a-tubulin, and for GAP-43, two genes whose expression levels in retinal ganglion cells (RGC) tend to correlate with growth. We first determined that most adult rat RGCs can retrogradely transport BDNF by injecting 125 I-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 for GAP-43 and Ta1. Axotomy alone resulted in a general decrease in Ta1 a-tubulin mRNA levels by 2 weeks, and elicited an increase in GAP-43 mRNA levels in an average of 30% of surviving RGCs. The intravitreal administration of a single dose of BDNF (5 mg) to axotomized RGCs on the day of injury did not affect Ta1 a-tubulin mRNA levels, but was followed by a moderate (approximately 80%), and short-lasting enhancement of GAP-43 mRNA levels in most RGCs during the first week after axotomy. No significant increase in GAP-43 mRNA levels was observed when BDNF was injected into the uninjured eye. We conclude that BDNF specifically enhances GAP-43 but not Ta1 mRNA levels in injured RGCs. Because BDNF is known to stimulate branch length of injured RGCs, we suggest that changes in the expression of GAP-43, but not Ta1 tubulin, correlate with branching of injured neurons as opposed to long distance regrowth.