A Potential Protective Role of RGS2 in Oxidative‐Stress Mediated Anxious Behavior in Rats

Abstract

A single nucleotide polymorphism in Regulator of G‐Protein Signaling (RGS)‐2 gene in human and its knockout in mice have been linked to panic disorder and anxiety, respectively. Interestingly, oxidative stress is proposed to be involved in anxiety. The present study is the first to provide a link between RGS2, oxidative stress and anxiety. Our neuronal cell culture studies demonstrate that 1h H2O2 treatment increases while 4h H2O2 treatment decreases RGS2 and antioxidant proteins. RGS2 antisense treatment prevented the increase in antioxidant protein expression suggesting the involvement of RGS2 in this process. Oxidant producing pharmacological agent BSO treatment for 4 and 7 d in rats, increased the levels of oxidative stress markers, protein nitrotyrosine and MDA, in the brain regions implicated in the anxiety response. This was accompanied by a decrease in RGS2 and antioxidant proteins especially, glutathione reducatse 1 and Glyoxalase 1, the proteins previously implicated in the development of anxiety. Two day BSO treatment increased RGS2 and antioxidant protein expression. Furthermore, behavior tests revealed that 4 and 7 d BSO treated rats were more anxious than control or antioxidant, tempol treated rats while 2d treatment did not result in increased anxiety. Our studies suggest an involvement of oxidative stress in anxiety and a novel role of RGS2 in antioxidant homeostasis. [Funding: GEAR, UH].