Telmisartan Activates PPARδ 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 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.

Effects of stress on behavior and resting-state fMRI in rats and evaluation of Telmisartan therapy in a stress-induced depression model

“…For the tests of OFT and SPT, we found a trend for telmisartan to improve the decreased locomotor activity and sucrose preference, although these were not significant. A previous study showed that the treatment with telmisartan of 1 mg/kg for five weeks could notably improve the depressive symptoms in the stress mouse model [ 33 ]. Hence, the not significant effect may be due to the short treatment time and a relatively small dose for rats.…”

Effects of Baihe Dihuang powder on chronic stress depression rat models

“…Open-filed test (Li et al, 2017, Kuang et al, 2016): The device is a vertical square open box, 40 cm high, 80 cm long and 80 cm wide. The surrounding wall and the bottom surface are black, and the bottom surface is composed of 25 pieces of equal area, divided by white lines.…”

Evaluation of antidepressant effect of angiotensin receptor blocker telmisartan in albino mice

“…10 Another study showed that telmisartan has an effect on improving the PPAR delta receptors and also increasing the hippocampal activity of PPAR thereby improving depression. 11 A study by Wang et al mentioned telmisartan as a very promising neuroprotective compound and substantiates the therapeutic use of this drug in neurodegenerative diseases and traumatic brain disorders where glutamate neurotoxicity plays a significant role. 12 Saavedra et al mentions that the use of sartans may be beneficial for the treatment of many brain disorders.…”