Regulation of neuronal death and calcitonin gene-related peptide by fibroblast growth factor-2 and FGFR3 after peripheral nerve injury: Evidence from mouse mutants

Abstract

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.