Expression of fibroblast growth factor‐2 in hypoglossal motoneurons is stimulated by peripheral nerve injury

Abstract

We have studied the expression of basic fibroblast growth factor 2 (FGF-2) and FGF receptor 1 (FGFR1) in the hypoglossal motor system during degeneration and regeneration by using an RNase protection assay, in situ hybridization, and Western blot analysis. The FGF-2 transcript was found to be weakly expressed in the hypoglossal motoneurons of the adult rat. Both peripheral transection and crush injury of the hypoglossal nerve resulted in a marked up-regulation of the FGF-2 mRNA in motoneurons of the hypoglossal nucleus (with a peak at 10 and 11 days postlesion) as well as in the proximal and distal nerve stumps. The FGFR1 transcript was strongly expressed by hypoglossal motoneurons of unlesioned rats. Neither axotomy nor crush lesion of the hypoglossal nerve revealed any alteration of the expression level and cellular localization in the hypoglossal nucleus, but they did result in a significant increase of the FGFR1 mRNA level in the proximal and distal nerve stump. Western blot analysis of the hypoglossal nucleus revealed the presence of the 21 kD and 23 kD isoforms and of a weak expression of the 18 kD isoform. Hypoglossal nerve transection resulted in a complete down-regulation of the FGF-2 protein 3 days after lesion. After 14 days, however, the level of the three isoforms was increased above the control level. The regulation of FGF-2 in hypoglossal motoneurons after experimental nerve injury is in agreement with the idea of a lesion-related function of FGF-2. Together with previously reported neurotrophic effects, these results suggest that FGF-2 provides trophic support for lesioned motoneurons. At the injury site, FGF-2 could be involved in the regulation of the myelination.

The role of basic fibroblast growth factor in peripheral nerve regeneration

“…FGFs promote mitogenesis of mesoderm-and neuroectodermderived cells and are involved in regulating diverse processes like proliferation and differentiation during embryonic development and mediate effects in the adult organism on maintenance and during tissue repair (Böhlen, 1989). In the central nervous system, FGF-2 is found to be expressed in glial cells and distinct neuronal populations (Gonzalez et al 1995;Grothe et al 1991;Huber et al 1997). Regarding the activities, FGF-2 stimulates mitogenesis and differentiation of neuronal precursors and glial cells (Ray et al 1997) and mediates neurotrophic and neurite outgrowth effects in the injured central nervous system (Grothe and Wewetzer 1996;Grothe et al 1999).…”

The spinal muscular atrophy gene product regulates neurite outgrowth: importance of the C terminus

“…Further, SMN interacts with an intracellular isoform of fibroblast growth factor 2 (FGF‐2) and is associated with at least a subset of snRNPs (24, 25). In motoneurons, endogenous FGF‐2 is expressed and exhibits neurotrophic activity after exogenous application (26, 27), indicating the importance of the SMN/FGF‐2 complex for the survival and regeneration of these cells.…”

Preserved expression of fibroblast growth factor (FGF)-2 and FGF receptor 1 in brain and spinal cord of amyotrophic lateral sclerosis patients

“…While FGF-2 and FGFR1 expression has been previously described to be mostly neuronal in the spinal cord and motor nuclei of the brain (Grothe et al 1991a;GomezPinilla et al 1992;Gonzalez et al 1995;Grothe and Wewetzer 1996;Huber et al 1997), upregulation of FGF-2 in non-neuronal cells such as astrocytes and microglia has been observed in the CNS after traumatic or toxic stimuli do Carmo Cunha et al 2007). In our study, however, FGF-2-expression remained predominantly neuronal in end stage ALS tissue, and staining of adjacent sections of the hypoglossal nucleus with the astrocyte marker GFAP did not reveal colocalization.…”

“…Several Wndings support this concept, like (1) speciWc retrograde transport of iodinated FGF-2 after injection into the muscle (Grothe and Unsicker 1992), (2) decreased FGF-2 immunoreactivity in hypoglossal motoneurons during the Wrst week after hypoglossal nerve transection (Grothe and Unsicker 1992), and (3) loss of FGF-2 immunoreactivity in hypoglossal motoneurons after colchicine treatment (Grothe and Janet 1995). In addition, FGF-2 protein and mRNA are localized to motor nuclei of the brain stem and spinal cord (Grothe et al 1991a;Gonzalez et al 1995;Grothe and Wewetzer 1996;Huber et al 1997). FGF-2 eVects are mediated via low-aYnity binding sites represented by heparan sulphate proteoglycans (McKeehan et al 1998) and four high-aYnity tyrosine transmembrane receptors (FGF receptors, FGFR), which belong to the immunoglobulin superfamily and are encoded by distinct genes with diVerent splice variants (Klagsbrun and Baird 1991;Jaye et al 1992).…”

“…FGF-2 eVects are mediated via low-aYnity binding sites represented by heparan sulphate proteoglycans (McKeehan et al 1998) and four high-aYnity tyrosine transmembrane receptors (FGF receptors, FGFR), which belong to the immunoglobulin superfamily and are encoded by distinct genes with diVerent splice variants (Klagsbrun and Baird 1991;Jaye et al 1992). At least FGFR1 protein and mRNA were found in brainstem nuclei including motoneurons (Wanaka et al 1990;Gonzalez et al 1995;Huber et al 1997).…”