We have examined the cellular distribution of both FGF-2 and FGFR1 imm
unoreactivity and their mRNAs throughout the normal adult rat brain in
order to reconcile numerous disparate findings in the published liter
ature. The results confirm a widespread distribution of FGF-2 and FGFR
1 in the rat brain, and different regions express distinct patterns of
FGF-2 and FGFR1 mRNA and protein: neuronal and non-neuronal cells sho
w different subcellular distributions that vary according to the area
where they are located. The intensity of the staining and hybridizatio
n also varies according to the loci examined and the cell type involve
d. Astrocytes contain the highest levels of FGF-2 and FGFR1 mRNAs, and
characteristically, possess high levels of immunoreactive FGF-2 withi
n the nucleus. Amongst non-neuronal cells, oligodendrocytes do not syn
thesize or contain significant levels of FGF-2 immunoreactivity howeve
r, they do express FGFR1 mRNA. In these cells, immunoreactive FGFR1 is
mainly associated with the myelin sheaths of neuronal fibers. In vent
ricular systems, ependymal cells synthesize and contain immunoreactive
FGFR1. In contrast, only cells lining the lateral wall of the IIIrd v
entricle express FGF-2 mRNA. Subependymal cells contain high levels of
both FGF-2 and FGFR1 immunoreactivity. Neurons express low levels of
FGF-2 mRNA and immunoreactive FGF-2 is localized predominantly to the
perikaryon. However, selected populations of neurons, such as CA2 fiel
d of the hippocampus, show high levels of FGF-2 mRNA, in which the nuc
leus is strongly immunopositive, Similarly, high levels of FGFR1 mRNA
are localized to select populations of neurons (e.g. amygdala). FGFR1
immunoreactivity is mainly associated with myelinated fiber tracts (e.
g. striatum), and some neurons show immunoreactivity in the perikaryon
(e.g. hippocampus), the nucleus (e.g. mesencephalic trigeminal nucleu
s), or in axonal projections (e.g. hypothalamus). Remarkably, in many
of the areas studied, FGF-2 and FGFR1 mRNA and/or their translated pro
tein do not co-localize in neurons (e.g. neo-cortices) or even in the
same regions of the brain (e.g. substantia nigra). In other instances,
mRNAs for both FGF-2 and FGFR1 colocalize (e.g. supraoptic nucleus).
The brain, in contrast to peripheral tissues, contains high levels of
FGF-2 and actively expresses its gene under normal physiological condi
tions. The highly specific anatomical distribution of immunoreactive F
GF-2 in neuronal and non-neuronal brain cells, supports the notion tha
t it plays a multifunctional role in the CNS under normal physiology.
By correlating the localization and the synthesis of FGF-2 and one of
its high affinity receptors, FGFR1, in the CNS, it should be possible
to obtain a better understanding of the roles of FGF-2 in normal and p
athological conditions.