Dynamic regulation of cerebral DNA repair genes by psychological stress.
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 (6 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.
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Psychiatric Centre Copenhagen, Rigshospitalet Afs. 6102, DK-2100 Copenhagen, Denmark. Electronic address: forsberg.kristin@gmail.com.
Kristin
K
Forsberg
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Psychiatric Centre Copenhagen, Rigshospitalet Afs. 6102, DK-2100 Copenhagen, Denmark.
Nadia
N
Aalling
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Psychiatric Centre Copenhagen, Rigshospitalet Afs. 6102, DK-2100 Copenhagen, Denmark; Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5, P.O. Box 2099, 1014 Copenhagen K, Denmark.
Gitta
G
Wörtwein
Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5, P.O. Box 2099, 1014 Copenhagen K, Denmark.
Steffen
S
Loft
Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5, P.O. Box 2099, 1014 Copenhagen K, Denmark.
Peter
P
Møller
Department of Experimental Medicine, Faculty of Health and Medical Sciences, University of Copenhagen & Rigshospitalet; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Jann
J
Hau
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Psychiatric Centre Copenhagen, Rigshospitalet Afs. 6102, DK-2100 Copenhagen, Denmark; Psychiatric Centre Copenhagen, University Hospital of Copenhagen, Edel Sauntes Allé 10, DK-2100 Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Ida
I
Hageman
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Psychiatric Centre Copenhagen, Rigshospitalet Afs. 6102, DK-2100 Copenhagen, Denmark; Psychiatric Centre Copenhagen, University Hospital of Copenhagen, Edel Sauntes Allé 10, DK-2100 Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Martin B
MB
Jørgensen
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Psychiatric Centre Copenhagen, Rigshospitalet Afs. 6102, DK-2100 Copenhagen, Denmark; Psychiatric Centre Copenhagen, University Hospital of Copenhagen, Edel Sauntes Allé 10, DK-2100 Copenhagen, Denmark.
Anders
A
Jørgensen
D000818:Animals; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism* / Q000503:physiopathology
D045643:DNA Repair Enzymes
Comet assay; DNA repair; Hippocampus; Oxidative stress; Prefrontal cortex; Stress