Hypoxic induction of vascular endothelial growth factor is selectively impaired in mice carrying the mutant SOD1 gene

Tetsuro Murakami, Hristelina Ilieva, Mito Shiote, Tetsuya Nagata, Isao Nagano, Mikio Shoji, Koji Abe

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)231-237
Number of pages7
JournalBrain Research
Volume989
Issue number2
DOIs
Publication statusPublished - Nov 7 2003

Keywords

  • Hypoxic induction
  • Mouse
  • SOD1 gene
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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