Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8456434 | Mutation Research/Genetic Toxicology and Environmental Mutagenesis | 2015 | 7 Pages |
Abstract
Neuronal genotoxic insults from oxidative stress constitute a putative molecular link between stress and depression on the one hand, and cognitive dysfunction and dementia risk on the other. Oxidative modifications to DNA are repaired by specific enzymes; a process that plays a critical role for maintaining genomic integrity. The aim of the present study was to characterize the pattern of cerebral DNA repair enzyme regulation after stress through the quantification of a targeted range of gene products involved in different types of DNA repair. 72 male Sprague-Dawley rats were subjected to either restraint stress (6Â h/day) or daily handling (controls), and sacrificed after 1, 7 or 21 stress sessions. The mRNA expression of seven genes (Ogg1, Ape1, Ung1, Neil1, Xrcc1, Ercc1, Nudt1) involved in the repair of oxidatively damaged DNA was determined by quantitative real time polymerase chain reaction in the prefrontal cortex (PFC) and hippocampus (HC). DNA repair gene expression in PFC exhibited a general trend towards an induction after acute stress and a decrease after subchronic exposure compared to control animals. After chronic stress, a normalization towards control levels was observed. A similar pattern was seen in HC, but with overall smaller effects and without the induction after acute stress. Nuclear DNA damage from oxidation as measured by the comet assay was unaffected by stress in both regions. We conclude that psychological stress have a dynamic influence on brain DNA repair gene expression; however, since we were unable to identify concurrent changes in DNA damage from oxidation, the down-stream consequences of this regulation, if any, remains unclear.
Keywords
endonuclease VIII-like 1X-Ray Repair Cross-Complementing Protein 1PFCUNG1RT-PCNEIL1BERNUDIXSSBRXRCC1APE1OGG18-oxoguanine glycosylase 1apurinic/apyrimidinic endonuclease 1NERROSStressDNA repairSingle strand break repairnucleotide excision repairbase excision repairOxidative stressComet assayprefrontal cortexHPA-axisHypothalamic-pituitary-adrenal axisHippocampusERCC1Reactive oxygen species
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Authors
Kristin Forsberg, Nadia Aalling, Gitta Wörtwein, Steffen Loft, Peter Møller, Jann Hau, Ida Hageman, Martin B. Jørgensen, Anders Jørgensen,