title: Chronic restraint stress in rats causes sustained increase in urinary corticosterone excretion without affecting cerebral or systemic oxidatively generated DNA/RNA damage.
abstract: Increased oxidatively generated damage to nucleic acids (DNA/RNA) may be a common mechanism underlying accelerated aging in psychological stress states and mental disorders. In the present study, we measured the urinary excretion of corticosterone and markers of systemic oxidative stress on nucleic acids, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively, in rats subjected to chronic restraint stress. To reliably collect 24h urine samples, the full 3-week restraint stress paradigm was performed in metabolism cages. We further determined frontal cortex and hippocampal levels of oxidatively generated nuclear DNA damage, as measured by oxoguanine DNA glycosylase and formamidopyrimidine DNA glycosylase sensitive sites detected by the comet assay, as well as the expression of genes involved in DNA repair (Ogg1 and Nudt1) and inflammation (Ccl2 and Tnf). The metabolism cage housing in itself did not significantly influence a range of biological stress markers. In the restraint stress group, there was a sustained 2.5 fold increase in 24h corticosterone excretion from day 2 after stress initiation. However, neither whole-body nor cerebral measures of nucleic acid damage from oxidation were affected by stress. In contrast, cerebral DNA repair enzymes exhibited a general trend towards an induction, which was significant for hippocampal Nudt1. The results and their implications for stress sensitivity and resilience are discussed.
authors.affiliation: Psychiatric Centre Copenhagen, University Hospital of Copenhagen, Denmark. anders.01.joergensen@regionh.dk
authors.forename: Anders
authors.initials: A
authors.lastname: Jorgensen
authors.forename: Katrine
authors.initials: K
authors.lastname: Maigaard
authors.forename: Gitta
authors.initials: G
authors.lastname: Wörtwein
authors.forename: Ida
authors.initials: I
authors.lastname: Hageman
authors.forename: Trine
authors.initials: T
authors.lastname: Henriksen
authors.forename: Allan
authors.initials: A
authors.lastname: Weimann
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.forename: Jann
authors.initials: J
authors.lastname: Hau
authors.forename: Henrik Enghusen
authors.initials: HE
authors.lastname: Poulsen
authors.forename: Martin Balslev
authors.initials: MB
authors.lastname: Jorgensen
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003345:Corticosterone / Q000652:urine*; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D014409:Tumor Necrosis Factor-alpha; D045647:DNA Glycosylases; C483741:OGG1 protein, rat; D003345:Corticosterone