| Summary: | Regeneration of PNS neurons is accompanied by the expression of regeneration
associated genes, including trophic factors and their receptors. In contrast, this gene expression
is not maintained in CNS neurons, which undergo atrophy and/or death after axotomy. The
latter phenomenon may involve discrepancies in trophic support to the injured neurons. I
hypothesize that FGF-2, FGFR-1 and/or FGFR-2 mRNA and protein are increased in
axotomized facial (PNS) motoneurons, and fail to be upregulated in axotomized
rubrospinal (CNS) neurons. In situ hybridization (ISH), reverse transcriptase Polymerase
Chain Reaction (RT-PCR), immunohistochemistry and Western blots were used to study the
production of the neurotrophic factor FGF-2 and its receptors FGFR-1 and FGFR-2 in the facial
and red nucleus after axotomy of neurons in these nuclei.
ISH demonstrated large increases in FGF-2 mRNA expression and moderate increases of
FGFR-1 mRNA in axotomized motoneurons of the facial nucleus. In contrast, no increase in
FGF-2 mRNA was detected in axotomized rubrospinal neurons, and the increase in FGFR-1
mRNA was transient. FGFR-2 mRNA expression in facial and red nuclei was limited to glial
cells. These data were corroborated by RT-PCR.
Immunohistochemistry for FGF-2 in the axotomized facial nucleus revealed increased
staining in the neuropil and some glial and neuronal profiles. Immunoreactivity for FGFR-1
increased in the facial nucleus motoneurons after axotomy, and declined in red nucleus neurons.
Immunoreactivity for FGFR-2 in the facial nucleus decreased in neurons after axotomy, and
increased in glial cells; in the red nucleus, neuronal staining remained unchanged.
Western blots revealed increased amounts of FGF-2 protein in the facial nucleus after
axotomy.
Thus, the main finding is that FGF-2 and FGFR-1 expression increased in axotomized
facial motoneurons, but decreased in rubrospinal neurons. These results suggest that FGF-2 in
the axotomized facial neuron may facilitate regeneration - most likely by acting via intracrine
and auto-/paracrine routes. The lack of expression of FGF-2 in axotomized rubrospinal neurons
may contribute to the failure of these neurons to regenerate. Moreover, the inability of
rubrospinal neurons to express FGFR-1 may be a critical factor in their failure to regenerate,
since FGFR-1 is involved in N-CAM/L1 mediated axon outgrowth. === Science, Faculty of === Zoology, Department of === Graduate
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