title: FGF-2 in the MPTP model of Parkinson's disease: effects on astroglial cells.
abstract: Fibroblast growth factor (FGF) is synthesized and stored by astroglial cells and regulates their proliferation and differentiation in vitro. Its implication in the transformation of quiescent astrocytes into reactive astroglia has been discussed. Using a mouse model of Parkinson's disease, in which FGF-2 has been shown to exert marked neuroprotection of nigrostriatal dopaminergic neurons, we have studied striatal levels of glial fibrillary acidic protein (GFAP), an established marker for astrocytes, and the distribution and morphologies of GFAP-immunoreactive cells following treatments with the neurotoxic drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the growth factor FGF-2, and the non-trophic control protein cytochrome C (cyt C). Systemic injections of MPTP (30 mg/kg) on 3 consecutive days, which we have previously shown to cause profound and long-lasting damage to the nigrostriatal system, induced an approximate 20% transient increase in striatal GFAP, determined by enzyme-linked immunosorbent assay (ELISA), 1 day after the final MPTP injection (= day 4), with subsequent normalization at day 7, which lasted until the end of the experiment (day 18). Morphologically, MPTP elicited a marked increase in number, size, arborization, and stainability of GFAP-immunoreactive cells at day 4 in a striatal area adjacent to the corpus callosum, which was evaluated throughout all experiments. Even on day 18, astrocytes were still apparently larger and more branched than in unlesioned controls. Administration of 4 micrograms of either FGF-2 or cyt C (soaked into a piece of Gelfoam unilaterally to the right striatum in either MPTP- or saline-injected controls) increased striatal GFAP levels bilaterally about 2- to 2.5-fold at 14 days, when FGF-2 showed marked protection of dopaminergic parameters. Likewise, GFAP immunocytochemistry revealed increased numbers of intensely immunoreactive astrocytes under any experimental situation. Differences in the morphologies of astrocytes in FGF-2- and cyt C-treated animals were very subtle and only noted at greater distances away from the site of application of the factors. We conclude that FGF-2, a potent neurotrophic factor for the neurotoxically lesioned nigrostriatal system, does not cause a marked astrogliotic reaction, which might be expected from previous in vitro and in vivo studies in other neural systems. This may limit concerns regarding potential applicability of FGF-2 to the parkinsonian striatum.
authors.affiliation: Department of Anatomy and Cell Biology, University of Heidelberg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Otto
authors.forename: K
authors.initials: K
authors.lastname: Unsicker
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D005346:Fibroblast Growth Factors; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine