The effects of fibroblast growth factors (FGFs) in vitro include the stimulation of mitogenesis in a variety of non-neuronal cell types and the promotion of the survival of various central and peripheral neuronal populations. The precise physiological role of FGFs in vivo is currently not known. As a step toward understanding the role of FGFs in the nervous system, the present study determined the distribution of acidic FGF (aFGF) in the rat CNS. The levels of aFGF in dissected areas of the nervous system were quantified using a biological assay method, and the cellular distribution of aFGF was determined in tissue sections using immunohistochemical methods. aFGF was found to be localized within specific neuronal populations in the CNS and was absent from non-neuronal cells. Neurons containing aFGF immunoreactivity included magnocellular neurons in the septal area and nucleus basalis; some additional defined neuronal groups in the subcortical telencephalon; specific neuronal populations in the hypothalamus, the thalamus, the substantia nigra, the reticular formation, and the pons; and motor and sensory neurons. Cerebral cortex and hippocampus contained only a very limited number of aFGF-immunoreactive neurons. A significant overlap of neuronal populations known to express the low-affinity NGF receptor (LNGFR) with populations containing aFGF immunoreactivity was also observed. These neuronal populations are known to be affected by neurodegenerative diseases, and the possible functional implications of the presence of aFGF and the LNGFR in these cells are discussed.
Acidic and basic fibroblast growth factors (aFGF and bFGF, respectively) are expressed in high levels in adult central nervous system (CNS). We report the time course of developmental appearance and distribution of these factors and of two FGF receptors, FGFR-1 and FGFR-2, in the CNS of rats ranging in age from embryonic day 16 to adult. Immunohistochemical analysis showed that sensory neurons in the midbrain were the first cells to contain detectable aFGF immunoreactivity at embryonic day 18. The next cell group to contain aFGF were motor neurons, which were found to be aFGF-positive at the day of birth. A number of other subcortical neuronal populations were observed to contain aFGF immunoreactivity after postnatal day 7. Adult levels and distribution patterns of aFGF were reached in all CNS areas by postnatal day 28. Basic FGF immunoreactivity was observed at postnatal day 0 in neurons in the CA2 subfield of hippocampus. Astrocytes contained detectable bFGF immunoreactivity, starting at postnatal day 7. Adult levels and patterns of distribution of bFGF were reached in all CNS areas by postnatal day 28. These immunohistochemical observations were confirmed by using bioassay and Western blot techniques. FGFR-1 and FGFR-2 mRNA were expressed in significant levels in all CNS areas at all time points analyzed. The observation that aFGF and bFGF appear in specific and distinct cellular populations at relatively late developmental times suggests that these FGFs may be involved in specific mechanisms of CNS maturation, maintenance, and repair.
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