Changes in PPARδ expression in a rat model of stress‐induced depression

Abstract

Depression is a common mental disorder that has been linked to a decrease in the expression of serotonin and/or the serotonin transporter in the brain. Antidepressants that target the monoaminergic system are widely used in the clinical setting. Peroxisome proliferator-activated receptor δ (PPAR δ) overexpression or activation is thought to improve depression-like behaviours in rodents. The present study was designed to characterize the changes in PPARδ expression in the hippocampus in rats with stress-induced depression. We used an unpredictable chronic mild stress (CMS) model in rats to study the role of PPARδ in the hippocampus. Behaviour was evaluated via a forced swim test (FST), a tail suspension test (TST), and a sucrose preference test (SPT). Then, the changes in PPARδ expression and other signals were determined using Western blots. We found that PPARδ expression in the hippocampus was markedly reduced in rats with depression. Moreover, the expression of the serotonin transporter was also significantly decreased. Treatment with a PPARδ agonist enhanced the expression of PPARδ and the serotonin transporter in the hippocampus of rats with stress-induced depression. Additionally, treatment with a PPARδ agonist increased the expression of the serotonin transporter in cultured hippocampal (H19-7) cells, and this action was ablated in the absence of PPARδ, which was attenuated with shRNA. Taken together, we found that PPARδ plays an important role in the regulation of serotonin transporter expression and that chronic stress may lower PPARδ expression in the brain via apoptosis and may attenuate serotonin transporter expression, thus inducing depression in rats.

Telmisartan Activates PPARδ to Improve Symptoms of Unpredictable Chronic Mild Stress-Induced Depression in Mice

“…Notably, the amelioration of the behavioral performance in the OFT and SPT, as well as hippocampal PPARδ and 5-HTT expression levels, induced by telmisartan was inhibited by a PPARδ antagonist, GSK0660. Furthermore, down regulation of PPARδ alone reproduced the phenotypes of the UCMS as indicated in our previous study 9 . In PPARδ knockdown mice with UCMS, the depression-like behavior was significantly higher than those mice infected with the scrambled shRNA.…”

“…PPARδ shows a widespread brain distribution, it is least two-fold more highly expressed in brain than in muscle 7 . Recently, 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 . Moreover, PPARδ activation also produces neuroprotection and reverses neurodegeneration in Alzheimer’s disease 10 , 11 , Parkinson’s disease 12 and Huntington’s disease 13 .…”

Hippocampal PPARα is a novel therapeutic target for depression and mediates the antidepressant actions of fluoxetine in mice

“…Also, two other members of the PPAR family, PPARβ/δ and PPARγ, have also been correlated with depression, directly or indirectly. For example, hippocampal PPARδ overexpression repressed the stress‐induced depressive‐like behaviours (Ji et al ., ), and decreased PPARδ expression was found in rats subjected to CUMS (Liu et al ., ,b). Both pioglitazone and rosiglitazone, two agonists of PPARγ, have potential antidepressant‐like effects (Eissa Ahmed et al ., ; Sadaghiani et al ., ).…”

“…Western blotting was performed according to a protocol used in other reports (Zhai et al ., ; Qin et al ., ; Liu et al ., , ,b; Han et al ., ; Huang et al ., ; Zhang et al ., ; Wang et al ., , ). Primary antibodies against PPARα (ab8934, 1:500; Abcam, Cambridge, UK), BDNF (sc‐20981, 1:200; Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA) and GAPDH (2118S, 1:2000; Cell Signaling, Danvers, MA, USA) were used.…”

The Chinese Herbal Formula PAPZ Ameliorates Behavioral Abnormalities in Depressive Mice

“…Repeated CORT injection in rodents have been considered as a reliable animal model for evaluating chronic stress depressive disorder [27]. The TST test is one of the classic experiments used to evaluate the anti-depression pharmacology of drugs and has often been used to observe the anti-depression effect of drugs by causing behavioral despair in animals [40,41]. In the present study, compared with the control group, a significant prolonged immobility time in the TST test was observed in the CORT-treated group mice.…”