Brain-derived neurotrophic factor modulates GAP-43 but not t?1 expression in injured retinal ganglion cells of adult rats

Abstract

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 Tα1 α‐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 125I‐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 Tα1. Axotomy alone resulted in a general decrease in Tα1 α‐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 μg) to axotomized RGCs on the day of injury did not affect Tα1 α‐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 Tα1 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 Tα1 tubulin, correlate with branching of injured neurons as opposed to long distance regrowth. J. Neurosci. Res. 47:561–572, 1997. © 1997 Wiley‐Liss, Inc.

Contributions of the Optic Tectum and the Retina as Sources of Brain-Derived Neurotrophic Factor for Retinal Ganglion Cells in the Chick Embryo

“…BDN F has been suggested to be a trophic factor derived from the tectum, and expression of BDN F mRNA in the tectum of several different species supports this hypothesis (Leibrock et al, 1989;Cohen-Cory and Fraser, 1994;). Attempts to demonstrate retrograde transport of NGF in this system failed (Yip and Johnson, 1983;C armignoto et al, 1989), although BDN F is transported from the tectum to the retina in adult rat (Fournier et al, 1997). Our data show that neurons of the retinorecipient layers of the optic tectum express BDNF, and we demonstrate, for the first time, that exogenously applied BDN F is transported from the tectum to the retina in the developing animal.…”

Neural Stem Cells Over-Expressing Brain-Derived Neurotrophic Factor (BDNF) Stimulate Synaptic Protein Expression and Promote Functional Recovery Following Transplantation in Rat Model of Traumatic Brain Injury

“…The intravitreal administration of a single dose of BDNF to axotomized RGCs on the day of injury caused a moderate and shortlasting enhancement in GAP-43 mRNA levels in most RGCs during the first week after axotomy. It was suggested that the changes in GAP-43 expression correlated with the branching of injured neurons [45]. Effects of BDNF on GAP-43 mRNA expression might be mediated by a Nitric Oxide (NO)-dependent mechanism [46].…”

Lens Injury Stimulates Axon Regeneration in the Mature Rat Optic Nerve

“…Developmentally, RGCs express this protein during axon outgrowth and synaptic refinement, then downregulate it as their connections mature (Skene and Willard, 1981b;Meiri et al, 1986;Moya et al, 1988). Normally, GAP-43 is transiently upregulated after axotomy and declines as RGCs undergo atrophic changes (Doster et al, 1991;Fournier et al, 1997;Wodarczyk et al, 1997;Wouters et al, 1998). Levels remain high only if regeneration is sustained (Skene and Willard, 1981a;Benowitz and Lewis, 1983;Doster et al, 1991;Meyer et al, 1994;Schaden et al, 1994;Berry et al, 1996).…”