title: Acute restraint stress induces rapid changes in central redox status and protective antioxidant genes in rats.
abstract: The stress-induced imbalance in reduction/oxidation (redox) state has been proposed to play a major role in the etiology of neurological disorders. However, the relationship between psychological stress, central redox state, and potential protective mechanisms within specific neural regions has not been well characterized. In this study, we have used an acute psychological stress to demonstrate the dynamic changes that occur in the redox system of hippocampal and striatal tissue. Outbred male Wistar rats were subject to 0 (control), 60, 120, or 240min of acute restraint stress and the hippocampus and striatum were cryodissected for redox assays and relative gene expression. Restraint stress significantly elevated oxidative status and lipid peroxidation, while decreasing glutathione ratios overall indicative of oxidative stress in both neural regions. These biochemical changes were prevented by prior administration of the glucocorticoid receptor antagonist, RU-486. The hippocampus also demonstrated increased glutathione peroxidase 1 and 4 antioxidant expression which was not observed in the striatum, while both regions displayed robust upregulation of the antioxidant, metallothionein 1a. This was observed with concurrent upregulation of 11β-hydroxysteroid dehydrogenase 1, a local reactivator of corticosterone, in addition to decreased expression of the cytosolic regulatory subunit of superoxide-producing enzyme, NADPH-oxidase. Together, this study demonstrates distinctive regional redox profiles following acute stress exposure, in addition to identifying differential capabilities in managing oxidative challenges via altered antioxidant gene expression in the hippocampus and striatum.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia 4072, Australia. Electronic address: j.spiers@uq.edu.au.
authors.forename: Jereme G
authors.initials: JG
authors.lastname: Spiers
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia 4072, Australia.
authors.forename: Hsiao-Jou Cortina
authors.initials: HJ
authors.lastname: Chen
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia 4072, Australia.
authors.forename: James S M
authors.initials: JS
authors.lastname: Cuffe
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia 4072, Australia.
authors.forename: Conrad
authors.initials: C
authors.lastname: Sernia
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia 4072, Australia.
authors.forename: Nickolas A
authors.initials: NA
authors.lastname: Lavidis
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D015870:Gene Expression / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis; D015735:Mifepristone / Q000494:pharmacology; D019255:NADPH Oxidases / Q000096:biosynthesis; D050983:NF-E2 Transcription Factor / Q000096:biosynthesis; D010084:Oxidation-Reduction; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D051381:Rats; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000097:blood / Q000378:metabolism*; D000094765:Glutathione Peroxidase GPX1
chemical_list: C491055:Mt2A protein, rat; D050983:NF-E2 Transcription Factor; D015735:Mifepristone; D008668:Metallothionein; D042842:11-beta-Hydroxysteroid Dehydrogenases; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; C523860:glutathione peroxidase 4, rat; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D005978:Glutathione; D003345:Corticosterone; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat
keywords: Acute stress; Glucocorticoid receptor; Glutathione peroxidase; Oxidative stress; RU-486; Redox status