title: Age-dependent guanine oxidation in DNA of different brain regions of Wistar rats and prematurely aging OXYS rats.
abstract: BACKGROUND
  Oxidative damage to the cell, including the formation of 8-oxoG, has been regarded as a significant factor in carcinogenesis and aging. An inbred prematurely aging rat strain (OXYS) is characterized by high sensitivity to oxidative stress, lipid peroxidation, protein oxidation, DNA rearrangements, and pathological conditions paralleling several human degenerative diseases including learning and memory deterioration.
  
  
  METHODS
  We have used monoclonal antibodies against a common pre-mutagenic base lesion 8-oxoguanine (8-oxoG) and 8-oxoguanine DNA glycosylase (OGG1) in combination with indirect immunofluorescence microscopy and image analysis to follow the relative amounts and distribution of 8-oxoG and OGG1 in various cells of different brain regions from OXYS and control Wistar rats.
  
  
  RESULTS
  It was shown that 8-oxoG increased with age in mature neurons, nestin- and glial fibrillary acidic protein (GFAP)-positive cells of hippocampus and frontal cortex in both strains of rats, with OXYS rats always displaying statistically significantly higher levels of oxidative DNA damage than Wistar rats. The relative content of 8-oxoG and OGG1 in nestin- and GFAP-positive cells was higher than in mature neurons in both Wistar and OXYS rats. However, there was no significant interstrain difference in the content of OGG1 for all types of cells and brain regions analyzed, and no difference in the relative content of 8-oxoG between different brain regions.
  
  
  CONCLUSIONS
  Oxidation of guanine may play an important role in the development of age-associated decrease in memory and learning capability of OXYS rats.
  
  
  CONCLUSIONS
  The findings are important for validation of the OXYS rat strain as a model of mammalian aging.
authors: SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia.
authors: Evgeniya A
authors: EA
authors: Sattarova
authors: Olga I
authors: OI
authors: Sinitsyna
authors: Elena A
authors: EA
authors: Vasyunina
authors: Alexander B
authors: AB
authors: Duzhak
authors: Nataliya G
authors: NG
authors: Kolosova
authors: Dmitry O
authors: DO
authors: Zharkov
authors: Georgy A
authors: GA
authors: Nevinsky
mesh_terms: D000375:Aging; D019588:Aging, Premature / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D015227:Lipid Peroxidation; D008568:Memory; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases; C483741:OGG1 protein, rat