ABSTRACT
Regulator of G-protein signaling protein (RGS)-2 is a modulator of anxiety and dysregulation of oxidative stress is implicated in anxiety. Also, RGS2 expression is reported to be induced by oxidative stress. Thus, if oxidative stress induces RGS2 expression and lack of RGS2 causes anxiety, then mechanisms that link RGS2 and oxidative stress potentially critical to anxiety must be revealed. Our study is the first to suggest role of RGS2 in regulation of enzymes involved in antioxidant defense namely glyoxalase-1 and glutathione reductase-1 via activation of p38 MAPK and PKC pathways in an Sp-1 dependent manner.
Subject(s)
Antioxidants/metabolism , Homeostasis , Neurons/metabolism , RGS Proteins/metabolism , Animals , Blotting, Western , Cell Line , Cell Survival/drug effects , DNA, Antisense/genetics , Enzyme Activation/drug effects , Gene Expression/drug effects , Glutathione Reductase/genetics , Glutathione Reductase/metabolism , Hydrogen Peroxide/pharmacology , Lactoylglutathione Lyase/genetics , Lactoylglutathione Lyase/metabolism , Mice , Neurons/cytology , Neurons/drug effects , Oxidants/pharmacology , Oxidative Stress/drug effects , Protein Carbonylation/drug effects , Protein Kinase C/metabolism , RGS Proteins/genetics , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Recent work has suggested correlation of oxidative stress with anxiety-like behavior. There also is evidence for anxiolytic effects of physical exercise. However, a direct role of oxidative stress in anxiety is not clear and a protective role of physical exercise in oxidative stress-mediated anxiety has never been addressed. In this study, we have utilized rats to test direct involvement of oxidative stress with anxiety-like behavior and have identified oxidative stress mechanisms likely involved in anxiolytic effects of physical exercise. Intraperitoneal injections at non-toxic dose of l-buthionine-(S,R)-sulfoximine (BSO), an agent that increases oxidative stress markers, increased anxiety-like behavior of rats compared to vehicle-treated control rats. Prior 2 weeks treatment with the antioxidant, tempol attenuated BSO-induced anxiety-like behavior of rats suggesting a role of oxidative stress in this phenomenon. Moreover, moderate treadmill exercise prevented BSO-induced anxiety-like behavior of rats and also prevented BSO-mediated increase in oxidative stress markers in serum, urine and brain tissue homogenates from hippocampus, amygdala and locus coeruleus. Thus increasing oxidative stress increases anxiety-like behavior of rats. Moreover, antioxidant or treadmill exercise training both reduce oxidative stress in the rat brain regions implicated in anxiety response and prevent anxiety-like behavior of rats.
