Antidepressant-like Effects of Fenofibrate in Mice Via the Hippocampal Brain-derived Neurotrophic Factor Signalling Pathway

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2016 Nov 19

PMID 27861729

Citations 39

Authors

Bo Jiang

Ying-Jie Wang

Hao Wang

Lu Song

Chao Huang

Qing Zhu

Feng Wu

Wei Zhang

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Depression is a neuropsychiatric disorder accompanied by a decrease in the brain-derived neurotrophic factor (BDNF) signalling cascade in the hippocampus. Fenofibrate is a selective agonist of PPAR-α. In this study, we investigated the antidepressant-like effects of fenofibrate in C57BL/6J mice.

Experimental Approach: The antidepressant-like effects of fenofibrate were first identified in the forced swim test (FST) and tail suspension test (TST), and then assessed in the chronic social defeat stress (CSDS) model. The changes in the hippocampal BDNF signalling pathway and adult hippocampal neurogenesis after CSDS and fenofibrate treatment were further investigated. A PPAR-α inhibitor, cannabinoid system inhibitors and BDNF signalling inhibitors were also used to determine the antidepressant mechanisms of fenofibrate.

Key Results: Fenofibrate administration exhibited antidepressant-like effects in the FST and TST without affecting the locomotor activity of mice. Chronic fenofibrate treatment also prevented the depressive-like symptoms induced by CSDS. Moreover, fenofibrate restored the CSDS-induced decrease in the hippocampal BDNF signalling cascade and adult hippocampal neurogenesis. The antidepressant-like effects of fenofibrate could be blocked by a PPAR-α inhibitor and BDNF signalling inhibitors.

Conclusions And Implications: Taken together, these results suggest that fenofibrate has antidepressant-like effects mediated through the promotion of the hippocampal BDNF signalling cascade.

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