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 mammali an CNS. Here, we characterized the effects of the survival-promoting neurot rophin brain-derived neurotrophic factor (BDNF) on mRNA expression of GAP-4 3, 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-expres sing RGCs. SC-1 expression remained unchanged. However, BDNF did not improv e long-distance axon regeneration into a peripheral nerve graft. Surprising ly, potentiating BDNF-mediated neuroprotection by simultaneous administrati on of a spin trap or a NOS inhibitor counteracted the BDNF-induced growth-a ssociated 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 me chanism. In summary, our data support the idea that survival and axon regen eration of lesioned CNS neurons can be regulated independently. (C) 2001 Ac ademic Press.