title: Hypoxic induction of vascular endothelial growth factor is selectively impaired in mice carrying the mutant SOD1 gene.
abstract: Localization and hypoxic induction of vascular endothelial growth factor (VEGF) was examined in the spinal cord of transgenic mice carrying a mutation in the superoxide dismutase 1 gene. Immunohistochemical and immunofluorescent study demonstrated that VEGF is mainly expressed in motor neurons before and after hypoxia. Baseline expression of VEGF was higher in transgenic (Tg) mice than in wild-type (Wt) littermates. However, VEGF was hardly induced after hypoxia in Tg mice, whereas Wt mice showed an approximate nine-fold increase. Impaired VEGF induction was evident in Tg mice at 12 weeks of age, when they were still presymptomatic. In contrast, baseline and hypoxic expression of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor did not differ between Tg and Wt mice. Thus, the present study demonstrates that hypoxic induction of VEGF in Tg mice is selectively impaired from a very early stage, suggesting profound involvement in the pathogenesis of motor neuron degeneration in this animal model of amyotrophic lateral sclerosis.
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Murakami
authors.forename: Hristelina
authors.initials: H
authors.lastname: Ilieva
authors.forename: Mito
authors.initials: M
authors.lastname: Shiote
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nagata
authors.forename: Isao
authors.initials: I
authors.lastname: Nagano
authors.forename: Mikio
authors.initials: M
authors.lastname: Shoji
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003720:Densitometry; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism*; D009154:Mutation; D009414:Nerve Growth Factors / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C495039:GDNF protein, human; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; C000606290:SOD1 protein, human; D042461:Vascular Endothelial Growth Factor A; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1