Increased oxidative damage to DNA in a transgenic mouse model of Huntington's disease.
Mitochondrial dysfunction and oxidative damage may play a role in the pathogenesis of Huntington's disease (HD). We examined concentrations of 8-hydroxy-2-deoxyguanosine (OH(8)dG), a well-established marker of oxidative damage to DNA, in a transgenic mouse model of HD (R6/2). Increased concentrations of OH(8)dG were found in the urine, plasma and striatal microdialysates of the HD mice. Increased concentrations were also observed in isolated brain DNA at 12 and 14 weeks of age. Immunocytochemistry showed increased OH(8)dG staining in late stages of the illness. These results suggest that oxidative damage may play a role in the pathogenesis of neuronal degeneration in the R6/2 transgenic mouse model of HD.
Bogdanov
M B
MB
Department of Neurology and Neuroscience, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY 10021, USA.
Andreassen
O A
OA
Dedeoglu
A
A
Ferrante
R J
RJ
Beal
M F
MF
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017551:Microdialysis; D008928:Mitochondria / Q000378:metabolism; D023421:Models, Animal; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010084:Oxidation-Reduction; D018384:Oxidative Stress
D015415:Biomarkers; C086055:HTT protein, human; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine