Basic fibroblast growth factor isoforms promote axonal elongation and branching of adult sensory neurons in vitro.
Synthesis of the multifunctional cytokine basic fibroblast growth factor (FGF-2) is up-regulated after sciatic nerve lesion. In this study, the effects of low and high molecular weight FGF-2 isoforms on axonal elongation and branching of dissociated rat sensory neurons derived from adult lumbar dorsal root ganglia were investigated. These neurons express FGF receptor (FGFR) type I in the cytoplasmic/membrane compartment and in nuclear speckles. FGF-2 isoforms increase the number of axonal branches in cultures obtained from control rats, but do not promote axonal elongation. In response to a preconditioning lesion, i.e. transection of the sciatic nerve 1 week before culture, the axonal length of ipsilateral lumbar sensory neurons increases two-fold when compared with non-lesioned control rats, and this response is significantly enhanced by FGF-2 isoforms but not by nerve growth factor (NGF). Neurons dissociated from ganglia located contralaterally to the lesion exhibit a smaller increase in axon elongation (30%). The stimulating effects of FGF-2 isoforms on axon growth are fully blocked, and the enhanced regeneration of prelesioned neurons is reduced by the FGFR inhibitor SU5402 suggesting an involvement of endogenous FGF signaling in response to a lesion. The present data support a direct neurotrophic role of the 18 kD and 23 kD FGF-2 isoforms on adult axonal regeneration which may be of therapeutic value in the treatment of peripheral nerve lesions. Furthermore, evidence is provided for an enhanced regenerative capacity not only of preaxotomized neurons but also of homonymous non-axotomized neurons.
Klimaschewski
L
L
Department of Neuroanatomy, Medical University of Innsbruck, Muellerstrasse 59, A-6020 Innsbruck, Austria. lars.lkimaschewski@uibk.ac.at
Nindl
W
W
Feurle
J
J
Kavakebi
P
P
Kostron
H
H
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology* / Q000502:physiology / Q000627:therapeutic use; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D020033:Protein Isoforms / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000188:drug therapy
D020033:Protein Isoforms; D016222:Fibroblast Growth Factor 2