Chronic hypoxia up-regulates fibroblast growth factor ligands in the perinatal brain and induces fibroblast growth factor-responsive radial glial cells in the sub-ependymal zone
Section snippets
Materials
The anti-serum against rat FGF2 was a generous gift from Pam Maher (Salk Institute) (Gonzales et al., 1995). The monoclonal anti-FGF1 antibody was a generous gift of Dr. Tom Maciag (Maine Center for Molecular Medicine). The polyclonal anti-FGFR-1 extracellular domain (Ab15), gift of L.T. Williams. The following antibodies were from commercial sources: monoclonal anti-FGFR-1 (Upstate Biotechnology, NY, USA); polyclonal anti-Flg (FGFR-1; Santa Cruz Biotechnology, Santa Cruz, CA, USA); mouse
FGF tissue levels increase after chronic postnatal hypoxia
To investigate the pattern of expression of the different molecular weight forms of FGF2 during postnatal development, western blot analyses were carried out in control rats after pre-absorption of FGF ligands to heparin–Sepharose beads. These analyses demonstrated that levels for each of the three molecular weight forms of FGF2 (18, 21.5 and 23 kDa), increased within the cerebral cortex over the course of postnatal development (Fig. 1). A steep increase in FGF2 levels occurred between birth
Discussion
In this study, we show that rats raised under conditions of chronic hypoxia during the early postnatal period have significantly higher levels of FGF1 and FGF2 within the brain. By contrast, chronic hypoxia does not increase the levels of the neurotrophins BDNF and NT-3. The up-regulation of FGF2 levels occurs within immature astroglia throughout the forebrain with the exception of the sub-ependymal zone. Chronic hypoxia induces the re-appearance of FGF receptors within ependymal cells, the
Acknowledgements
This work was supported by NIH Grants No. P01 NS35476, PO1 MH49351 and R01 NS37709-01A2. We wish to thank Dr. Ann Acheson and the Bioassay group at Regeneron Pharmaceuticals, for performing the ELISA, Dr. Y.-L. Li for expert technical assistance, Dr. T. Maciag and Dr. P. Maher for gifts of antibodies and Dr. A. Alvarez-Buylla, Dr. J. Leckman and Dr. L. Ment for critical discussions. We also thank anonymous reviewers for their suggestions and constructive criticism.
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