title: A chronic increase of corticosterone age-dependently reduces systemic DNA damage from oxidation in rats.
abstract: Stress and depression are associated with an acceleration of brain and bodily aging; effects which have been attributed to chronic elevations of glucocorticoids. We tested the hypothesis that a three week administration of stress-associated levels of corticosterone (CORT, the principal rodent glucocorticoid) would increase systemic and CNS DNA and RNA damage from oxidation; a phenomenon known to be centrally involved in the aging process. We also hypothesized that older individuals would be more sensitive to this effect and that the chronic CORT administration would exacerbate age-related memory decline. Young and old male Sprague-Dawley rats were non-invasively administered CORT by voluntary ingestion of nut paste containing either CORT (25mg/kg) or vehicle for a total of 22 days. CORT increased the 24h urinary excretion of the hormone to the levels previously observed after experimental psychological stress and caused a downregulation of the glucocorticoid receptor in the CA1 area of the hippocampus. Contrary to our hypothesis, 24h excretion of 8-oxodG/8-oxoGuo (markers of DNA/RNA damage from oxidation) was reduced in CORT-treated young animals, whereas old animals showed no significant differences. In old animals, CORT caused a borderline significant reduction of RNA oxidation in CNS, which was paralleled by a normalization of performance in an object location memory test. To our knowledge, this is the first demonstration that chronic stress-associated levels of CORT can reduce nucleic acid damage from oxidation. These findings contradict the notion of elevated CORT as a mediator of the accelerated aging observed in stress and depression.
authors.affiliation: Psychiatric Center Copenhagen (Rigshospitalet), Mental Health Services of the Capital Region of Denmark, Denmark; Laboratory of Neuropsychiatry, Psychiatric Center Copenhagen and Institute of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Denmark. Electronic address: anders.01.joergensen@regionh.dk.
authors.forename: Anders
authors.initials: A
authors.lastname: Jorgensen
authors.affiliation: Department of Experimental Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Otto
authors.initials: O
authors.lastname: Kalliokoski
authors.affiliation: Laboratory of Neuropsychiatry, Psychiatric Center Copenhagen and Institute of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Kristin
authors.initials: K
authors.lastname: Forsberg
authors.affiliation: Laboratory of Neuropsychiatry, Psychiatric Center Copenhagen and Institute of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Katrine
authors.initials: K
authors.lastname: Breitenstein
authors.affiliation: Laboratory of Clinical Pharmacology, Copenhagen University Hospital Rigshospitalet, Denmark; Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Weimann
authors.affiliation: Laboratory of Clinical Pharmacology, Copenhagen University Hospital Rigshospitalet, Denmark; Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Henriksen
authors.affiliation: Department of Experimental Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Jann
authors.initials: J
authors.lastname: Hau
authors.affiliation: Laboratory of Neuropsychiatry, Psychiatric Center Copenhagen and Institute of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Gitta
authors.initials: G
authors.lastname: Wörtwein
authors.affiliation: Laboratory of Clinical Pharmacology, Copenhagen University Hospital Rigshospitalet, Denmark; Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Denmark.
authors.forename: Henrik Enghusen
authors.initials: HE
authors.lastname: Poulsen
authors.affiliation: Psychiatric Center Copenhagen (Rigshospitalet), Mental Health Services of the Capital Region of Denmark, Denmark; Laboratory of Neuropsychiatry, Psychiatric Center Copenhagen and Institute of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Martin Balslev
authors.initials: MB
authors.lastname: Jorgensen
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D003345:Corticosterone / Q000008:administration & dosage* / Q000652:urine; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008568:Memory / Q000187:drug effects; D018384:Oxidative Stress; D051381:Rats
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D003345:Corticosterone
keywords: Aging; Depression; Glucocorticoids; Oxidatively generated nucleic acid damage; Stress