Telmisartan Activates PPAR? to Improve Symptoms of Unpredictable Chronic Mild Stress-Induced Depression in Mice.

ABSTRACT: Major depression is a common mental disorder that has been established to be associated with a decrease in serotonin and/or serotonin transporters in the brain. Peroxisome proliferator-activated receptor ? (PPAR?) has been introduced as a potential target for depression treatment. Telmisartan was recently shown to activate PPAR? expression; therefore, the effectiveness of telmisartan in treating depression was investigated. In unpredictable chronic mild stress (UCMS) model, treatment with telmisartan for five weeks notably decrease in the time spent in the central and the reduced frequency of grooming and rearing in open filed test (OFT) and the decreased sucrose consumption in sucrose preference test (SPT) compared with the paradigms. Telmisartan also reversed the decrease in PPAR? and 5-HTT levels in the hippocampus of depression-like mice. Administration of PPAR? antagonist GSK0660 and direct infusion of sh-PPAR? into the brain blocked the effects of telmisartan on the improvement of depression-like behavior in these mice. Moreover, telmisartan enhanced the expression of PPAR? and 5HTT in H19-7 cells. In conclusion, the obtained results suggest that telmisartan improves symptoms of stress-induced depression in animals under chronic stress through activation of PPAR?. Therefore, telmisartan may be developed as a potential anti-depressant in the future.

SUBMITTER: Li Y 

PROVIDER: S-EPMC5656622 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature