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

First Author  Warita H Year  2001
Journal  Brain Res Mol Brain Res Volume  89
Issue  1-2 Pages  147-52
PubMed ID  11311985 Mgi Jnum  J:134551
Mgi Id  MGI:3789243 Doi  10.1016/s0169-328x(01)00029-8
Citation  Warita H, et al. (2001) Oxidative damage to mitochondrial DNA in spinal motoneurons of transgenic ALS mice. Brain Res Mol Brain Res 89(1-2):147-52
abstractText  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.
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