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 δ (PPARδ) has been introduced as a potential target for depression treatment. Telmisartan was recently shown to activate PPARδ 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 PPARδ and 5-HTT levels in the hippocampus of depression-like mice. Administration of PPARδ antagonist GSK0660 and direct infusion of sh-PPARδ into the brain blocked the effects of telmisartan on the improvement of depression-like behavior in these mice. Moreover, telmisartan enhanced the expression of PPARδ 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 PPARδ. Therefore, telmisartan may be developed as a potential anti-depressant in the future.
Highlights
Peroxisome proliferator-activated receptors δ (PPARδ), as one of the receptors in the PPAR nuclear receptor family, is a ligand-activated transcription factor
Mice with unpredictable chronic mild stress (UCMS) showed less preference in sucrose intake, but the sucrose consumption was reversed in both telmisartan- and fluoxetine-treated groups [F(4,35) = 16.071, P < 0.05, Fig. 1E]
Losartan treatment did not affected Peroxisome proliferator-activated receptor δ (PPARδ) and 5-HTT expressions in UCMS mice. These results indicated that telmisartan effectively attenuates the adverse effect of stress on depression-like behavior, and this action seems different with other AT1 blockade, associated with increased PPARδ activation in the hippocampus
Summary
Peroxisome proliferator-activated receptors δ (PPARδ), as one of the receptors in the PPAR nuclear receptor family, is a ligand-activated transcription factor. PPARδ was shown to play an important role in repress stress-induced depressive behaviors[8] in addition to the regulation of serotonin transporter expression in hipopcampus[9]. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), is widely used to treat hypertension with the expectation of a decrease in the onset of cardiovascular and cerebrovascular disease. We investigated the effect of telmisartan on stress-induced depression in animals. The effect of telmisartan and losartan, a selective AT receptor antagonist, compared. The expression levels of PPARδ and 5-HTT in the hippocampus between vehicle-treated group and telmisartan-treatment group were determined in UCMS mice. The effects of telmisartan on expressions of PPARδ and 5-HTT were further studied in the H19-7 cell line
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