Neuroprotective Potential of Sodium Orthovanadate in a Mouse Model of Chronic Unpredictable Mild Stress.

Abstract

Depression is a psychiatric disorder characterized by low-esteem, anhedonia, social deficit, and lack of interest. Decreased BDNF and impaired TrKB signaling have been found to be associated in depression. Moreover, oxidative stress in the brain and subsequent reduction of BDNF have a prominent role in psychiatric disorders. In our study, depressive-like behavior was induced in mice by chronic unpredictable mild stress (CUMS) model. Further, sodium orthovanadate (SOV), a protein tyrosine phospahatase was used as a test drug as it is reported to stimulate BDNF levels. Sodium orthovanadate (SOV-5 mg/kg, 10 mg/kg) and fluoxetine (10 mg/kg) were given to mice orally for 21 days prior 30 minutes of stress induction. Various behavioral studies like tail suspension test (TST), open field test (OFT), and sucrose preference test (SPT); biochemical analyses for corticosterone, reduced glutathione (GSH), lipid peroxidation (LPO), superoxide dismutase (SOD), nitric oxide (NO) and ELISA for BDNF were performed. Body weight was measured on a weekly basis. The behavioral tests reflected depressive-like behavior in CUMS, which was attenuated by SOV and fluoxetine. SOV (10 mg/kg) significantly decreased malondialdehyde levels, NO, whereas increased GSH and SOD in both the cortex and hippocampus. Besides, ELISA revealed the elevation of BDNF levels in the treatment groups compared with the disease group (CUMS). Therefore, the treatment with SOV appeared to reverse both oxidative and nitrosative stress. Elevated BDNF level was associated with attenuation of depressive-like behaviors and serum corticosterone levels. The findings of this preliminary study indicates that SOV has potential to restore mood and social interaction in depression and so further molecular mechanisms will be warranted for clinical translation.