Regulation of neuronal death and calcitonin gene-related peptide by fibroblast growth factor-2 and FGFR3 after peripheral nerve injury: evidence from mouse mutants.
The presence and regulation of basic fibroblast growth factor and its high-affinity tyrosine kinase receptor FGFR3 in sensory neurons during development and after peripheral nerve injury suggest a physiological role of the fibroblast growth factor-2 system for survival and maintenance of sensory neurons. Here we investigated L5 spinal ganglia of intact and lesioned fibroblast growth factor-2 knock-out and FGFR3 knock-out mice. Quantification of sensory neurons in intact L5 spinal ganglia revealed no differences between wild-types and mutant mice. After sciatic nerve axotomy, the normally occurring neuron loss in wild-type mice was significantly reduced in both knock-out strains suggesting that fibroblast growth factor-2 is involved in neuronal death mediated via FGFR3. In addition, the number of chromatolytic and eccentric cells was significantly increased in fibroblast growth factor-2 knock-out mice indicating a transient protection of injured spinal ganglia neurons in the absence of fibroblast growth factor-2. The expression of the neuropeptide calcitonin gene-related peptide in sensory neurons of intact fibroblast growth factor-2 knock-out and FGFR3 knock-out mice was not changed in comparison to adequate wild-types. Fibroblast growth factor-2 wild-type and FGFR3 wild-type mice showed a lesion-induced decrease of calcitonin gene-related peptide-positive neurons in ipsilateral L5 spinal ganglia whereas the loss of calcitonin gene-related peptide-immunoreactive sensory neurons is reduced in the absence of fibroblast growth factor-2 or FGFR3, respectively. In addition, FGFR3 wild-type and knock-out mice displayed a contralateral reduction of the neuropeptide after axotomy. These results suggest that endogenous fibroblast growth factor-2 and FGFR3 are crucially involved in the regulation of survival and calcitonin gene-related peptide expression of lumbar sensory neurons after lesion, but not during development.
Jungnickel
J
J
Hannover Medical School, Department of Neuroanatomy, Germany. jungnickel.julia@mh-hannover.de
Klutzny
A
A
Guhr
S
S
Meyer
K
K
Grothe
C
C
D000818:Animals; D019771:Axotomy; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000172:deficiency* / Q000235:genetics; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000172:deficiency* / Q000235:genetics; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008161:Lumbosacral Region; D051379:Mice; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000378:metabolism* / Q000473:pathology; D012584:Sciatic Nerve / Q000293:injuries*
D051518:Fibroblast Growth Factor 3; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; D015740:Calcitonin Gene-Related Peptide