BDNF increases the number of axotomized rat retinal ganglion cells expressing GAP-43, L1, and TAG-1 mRNA--a supportive role for nitric oxide?
The death of neurons and the limited ability to activate growth-associated genes prevent the restoration of lesioned fiber tracts in the adult mammalian CNS. Here, we characterized the effects of the survival-promoting neurotrophin brain-derived neurotrophic factor (BDNF) on mRNA expression of GAP-43, L1, TAG-1, and SC-1 in axotomized and regenerating rat retinal ganglion cells (RGCs). BDNF led to de novo upregulation of TAG-1 mRNA in axotomized RGCs and to a threefold increase in the number of GAP-43 and L1 mRNA-expressing RGCs. SC-1 expression remained unchanged. However, BDNF did not improve long-distance axon regeneration into a peripheral nerve graft. Surprisingly, potentiating BDNF-mediated neuroprotection by simultaneous administration of a spin trap or a NOS inhibitor counteracted the BDNF-induced growth-associated gene expression. This led us to hypothesize that the BDNF effects on GAP-43, L1, and TAG-1 mRNA expression are mediated by a NO-dependent mechanism. In summary, our data support the idea that survival and axon regeneration of lesioned CNS neurons can be regulated independently.
Klöcker
N
N
Department of Neurology, University of Tübingen, Tübingen, 72076, Germany. nikolaj.kloecker@uni-tuebingen.de
Jung
M
M
Stuermer
C A
CA
Bähr
M
M
D000818:Animals; D019771:Axotomy; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015816:Cell Adhesion Molecules, Neuronal; D002470:Cell Survival / Q000187:drug effects; D058969:Contactin 2; D016166:Free Radical Scavengers; D019922:GAP-43 Protein / Q000378:metabolism*; D017403:In Situ Hybridization; D039841:Leukocyte L1 Antigen Complex; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000637:transplantation
D019208:Brain-Derived Neurotrophic Factor; D015816:Cell Adhesion Molecules, Neuronal; C548676:Cntn2 protein, rat; D058969:Contactin 2; D016166:Free Radical Scavengers; D019922:GAP-43 Protein; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D009569:Nitric Oxide