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

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


100 被引用数 (Scopus)


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.

ジャーナルMolecular Brain Research
出版ステータスPublished - 4月 18 2001

ASJC Scopus subject areas

  • 分子生物学
  • 細胞および分子神経科学


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