Brain-derived neurotrophic factor modulates GAP-43 but not T alpha1 expression in injured retinal ganglion cells of adult rats.
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 T alpha1 alpha-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 T alpha1. Axotomy alone resulted in a general decrease in T alpha1 alpha-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 microg) to axotomized RGCs on the day of injury did not affect T alpha1 alpha-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 T alpha1 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 T alpha1 tubulin, correlate with branching of injured neurons as opposed to long distance regrowth.
Fournier
A E
AE
Université de Montréal, Faculté de Médecine, Departement de Pathologie, Quebéc, Canada.
Beer
J
J
Arregui
C O
CO
Essagian
C
C
Aguayo
A J
AJ
McKerracher
L
L
D000818:Animals; D001345:Autoradiography; D001370:Axonal Transport; D019208:Brain-Derived Neurotrophic Factor / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D019922:GAP-43 Protein; D017403:In Situ Hybridization; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D016900:Neurofilament Proteins / Q000096:biosynthesis; D009900:Optic Nerve / Q000502:physiology*; D020221:Optic Nerve Injuries; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D012016:Reference Values; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects*; D014404:Tubulin / Q000096:biosynthesis*
D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014404:Tubulin