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

In order to clarify a possible role of oxidative stress in motoneuron death in amyotrophic lateral sclerosis (ALS), we examined a presence of 8-hydrox y-2-deoxyguanosine (8-OHdG), one of the best markers of the oxidative DNA d amage, in the spinal cord of transgenic mice harboring a mutant Cu/Zn super oxide dismutase (SOD1) gene. Immunocytochemistry showed a progressive accum ulation of 8-OHdG in ventral horn neurons from early and presymptomatic sta ge (25 weeks) before significant loss of ventral horn neurons, while no det ectable 8-OHdG in non-transgenic control mice. At the late and symptomatic stage (35 weeks), the 8-OHdG-like immunoreactivity spread over the posterio r horn of spinal cord in Tg mice. Thr immunoreactivity for 8-OHdG was not l ocalized 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, an d may be involved in the mechanism of the subsequent motoneuron death in th is model. (C) 2001 Elsevier Science B.V. All rights: reserved.