Hypoxic induction of vascular endothelial growth factor is selectively impaired in mice carrying the mutant SOD1 gene.
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.
Murakami
Tetsuro
T
Department of Neurology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Ilieva
Hristelina
H
Shiote
Mito
M
Nagata
Tetsuya
T
Nagano
Isao
I
Shoji
Mikio
M
Abe
Koji
K
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*
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