Oxidative damage to mitochondrial DNA in spinal motoneurons of transgenic ALS mice

Hitoshi Warita, Takeshi Hayashi, Tetsuro Murakami, Yasuhiro Manabe, Koji Abe

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

In order to clarify a possible role of oxidative stress in motoneuron death in amyotrophic lateral sclerosis (ALS), we examined a presence of 8-hydroxy-2-deoxyguanosine (8-OHdG), one of the best markers of the oxidative DNA damage, in the spinal cord of transgenic mice harboring a mutant Cu/Zn superoxide dismutase (SOD1) gene. Immunocytochemistry showed a progressive accumulation of 8-OHdG in ventral horn neurons from early and presymptomatic stage (25 weeks) before significant loss of ventral horn neurons, while no detectable 8-OHdG in non-transgenic control mice. At the late and symptomatic stage (35 weeks), the 8-OHdG-like immunoreactivity spread over the posterior horn of spinal cord in Tg mice. The immunoreactivity for 8-OHdG was not localized in the nucleus but in cytoplasm with small granular pattern. These data suggest that an oxidative damage to mitochondrial DNA is happening in spinal motoneurons of the Tg mice from very early stage of the disease, and may be involved in the mechanism of the subsequent motoneuron death in this model.

Original languageEnglish
Pages (from-to)147-152
Number of pages6
JournalMolecular Brain Research
Volume89
Issue number1-2
DOIs
Publication statusPublished - Apr 18 2001

Keywords

  • Amyotropic lateral sclerosis
  • Mitochondria
  • Oxidative stress
  • SOD1
  • Transgenic mouse

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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