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

ABSTRACT:

Background and purpose

Developing novel pharmacological targets beyond the monoaminergic system is now a popular strategy for treating depression. PPARα is a nuclear receptor protein that functions as a transcription factor,-regulating gene expression. We have previously reported that both WY14643 and fenofibrate, two pharmacological agonists of PPARα, have antidepressant-like effects in mice, implying that PPARα is a potential antidepressant target.

Experimental approach

We first used various biotechnological methods to evaluate the effects of chronic stress and fluoxetine on hippocampal PPARα. The viral-mediated genetic approach was then employed to explore whether hippocampal PPARα was an antidepressant target. PPARα inhibitors, PPARα-knockout (KO) mice and PPARα-knockdow

SUBMITTER: Song L 

PROVIDER: S-EPMC6016645 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature