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Regulator of G-protein signaling 5 protein protects against anxiety- and depression-like behavior

D'Souza, Manoranjan S.; Guisinger, Trevor C.; Norman, Haval; Seeley, Sarah L.; Chrissobolis, Sophocles

doi: 10.1097/FBP.0000000000000506
Research Reports

Anxiety and depression are a major health burden. Angiotensin II, via activation of angiotensin II type 1 receptor (AT1R)-mediated brain oxidative stress and inflammation may contribute to these emotional abnormalities. In this study, we investigated the role of a regulator of G-protein signaling 5 (RGS5) protein, which regulates AT1R activity, in angiotensin II-induced brain oxidative stress, inflammation and anxiety-, and depression-like behavior. We hypothesized that deletion of the RGS5 protein would worsen angiotensin II-induced anxiety- and depression-like behavior, cerebral vascular oxidative stress, and brain inflammation. Adult male wild-type and RGS5-deficient mice were implanted with osmotic minipumps delivering either vehicle (saline) or angiotensin II (1 mg/kg/d) for three weeks. Subsequently, mice were tested for locomotor activity, anxiety-like behavior (using the elevated plus maze), and depression-like behavior (using the tail suspension test). After behavioral testing, brain tissue was collected to assess oxidative stress and inflammatory proteins. RGS5 deletion resulted in anxiety-like but not depression-like behavior when compared to wild-type mice. Combined deletion of RGS5 and angiotensin II treatment did not further worsen anxiety-like behavior observed in RGS5-deficient mice. In contrast, depression-like behavior was worsened in RGS5-deficient mice treated with angiotensin II. Interestingly, RGS5 deficiency and angiotensin II treatment had no effect on cerebral vascular oxidative stress, or on expression of the inflammatory marker vascular cell adhesion molecule-1 in the brain. RGS5 deficiency was also associated with decreased blood pressure and an enhanced pressor response to angiotensin II. These data suggest that RGS5 protects against anxiety-like behavior and against angiotensin II-induced depression-like behavior.

Department of Pharmaceutical and Biomedical Sciences, Raabe College of Pharmacy, Ohio Northern University, Ada, Ohio, USA

Received 31 May 2019 Accepted as revised 19 August 2019

Correspondence to Sophocles Chrissobolis, PhD, Department of Pharmaceutical and Biomedical Sciences, Raabe College of Pharmacy, Ohio Northern University, 525 S. Main St., Ada, OH 45810, USA, e-mail:

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