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PMID: 12878680 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Functions of fibroblast growth factor (FGF)-2 and FGF-5 in astroglial differentiation and blood-brain barrier permeability: evidence from mouse mutants.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 23 ·No. 16 ·2003-07-23 ·Pages 6404-12

Reuss B, Dono R, Unsicker K

Abstract

Multiple evidence suggests that fibroblast growth factors (FGFs), most prominently FGF-2, affect astroglial proliferation, maturation, and transition to a reactive phenotype in vitro, and after exogenous administration, in vivo. Whether this reflects a physiological role of endogenous FGF is unknown. Using FGF-2 and FGF-5 single- and double mutant mice we show now a region-specific reduction of glial fibrillary acidic protein (GFAP), but not of S100 in gray matter astrocytes. FGF-2 is apparently the major regulator of GFAP, because in mice deficient for FGF-2, GFAP is distinctly reduced in cortex and striatum, whereas in FGF-5-/- animals only a reduction in the midbrain tegmentum can be observed. In FGF-2-/-/FGF-5-/- double mutant animals, GFAP-immunoreactivity is reduced in all three brain regions. Cortical astrocytes cultured from FGF-2-/-/FGF-5-/- double mutant mice revealed reduced levels of GFAP, but not S100 as compared with wild-type littermates. This phenotype could be rescued by exogenous FGF-2 but not FGF-5 (10 ng/ml). Electron microscopy revealed reduced levels of intermediate filaments in perivascular astroglial endfeet. This defect was accompanied by enhanced permeability of the blood-brain barrier (BBB), as detected by albumin extravasation. Levels of the tight junction proteins Occludin and ZO-1 were reduced in blood vessels of FGF-2-/-/FGF-5-/- double mutant mice as compared with wild-type littermates. Our data support the notion that endogenous FGF-2 and FGF-5 regulate GFAP expression in a region-specific manner. The observed defect in astroglial differentiation is accompanied by a defect in BBB function arguing for an indirect or direct role of FGFs in the regulation of BBB permeability in vivo.

MeSH Terms
Animals Astrocytes/cytology,metabolism Blood-Brain Barrier/genetics,physiology Brain/cytology,metabolism Cell Differentiation/physiology Fibroblast Growth Factor 2/metabolism Fibroblast Growth Factor 5 Fibroblast Growth Factors/metabolism Gene Expression Regulation/physiology Glial Fibrillary Acidic Protein/genetics,metabolism Intermediate Filaments/metabolism Membrane Proteins/biosynthesis Mice Mice, Knockout Mice, Mutant Strains Occludin Permeability Phosphoproteins/biosynthesis RNA, Messenger/metabolism S100 Proteins/metabolism Serum Albumin/metabolism Tight Junctions/metabolism Zonula Occludens-1 Protein
Chemicals
Fgf5 protein, mouse Glial Fibrillary Acidic Protein Membrane Proteins Occludin Ocln protein, mouse Phosphoproteins RNA, Messenger S100 Proteins Serum Albumin Tjp1 protein, mouse Zonula Occludens-1 Protein Fibroblast Growth Factor 2 Fibroblast Growth Factor 5 Fibroblast Growth Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Reuss Bernhard
Department of Neuroanatomy, IZN, University of Heidelberg, 69120 Heidelberg, Germany. [email protected]
Dono Rosanna
Unsicker Klaus
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Email
[email protected]
Published
2003-07-23
Pages
6404-12
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6740627
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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