DNA damage in brain may lead to cognitive dysfunctions and reduced longevity in WNIN/Ob obese rats

Abstract

AbstractBackgroundOne of the most common neurodegenerative diseases is Alzheimer’s disease where complex etiological alterations have been observed along with the typical pathology. Specifically, it has been proposed that epigenetic activation of specific genes due to other physiological conditions may also contribute to its pathology.MethodAgeing being one of the strongest risk factor where accumulation of DNA damage is rampant, we evaluated the extent in the brain of 15 months old WNIN/Ob obese rats. Early accumulation of DNA damage in brain can result in devastating genetic instability and wide array of physiological problems. WNIN obese rats have significantly reduced longevity (average lifespan of 15‐18 months). The extent of DNA damage in brain was studied as a hallmark of senescence in order to establish this rat as a model of aging related studies. DNA damage was assessed at the single cell level in neocortex and hippocampus of WNIN obese rats, WNIN lean littermates and normal WNIN controls at 3 and 15 months of age by Comet Assay. The samples were processed for neutral and alkaline electrophoresis, followed by fluorescent staining and analysis.ResultThe extent of DNA damage in the form of single‐strand breaks (SSBs) as well as double‐strand breaks (DSBs) in cells of neocortex and hippocampus of young WNIN obese rats was comparable with those seen in the 15 months old normal WNIN rats. Interestingly the extent of SSBs and DSBs in young WNIN lean littermates and WNIN controls were comparable.ConclusionOnset of significant DNA damage in different brain regions of obese rats at a much younger age is a plausible cause of reduced longevity observed in this novel obese rat model.