ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1595341
Antidepressant-like activity of Bezafibrate in mice models of depression: A behavioral and neurobiological characterization
Provisionally accepted
- 1Department of Orthopaedics, Second Affiliated Hospital of Nantong University, Nantong, China
- 2Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, Jiangsu Province, China
- 3Department of Neurosurgery, Second Affiliated Hospital of Nantong University, Nantong, China
- 4Department of Pharmacology, Pharmacy College, Nantong University, Nantong, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Depression represents a major global public health challenge, inflicting profound suffering on patients while imposing substantial socioeconomic burdens on families and healthcare systems. Although monoamine-based antidepressants remain first-line pharmacotherapy, accumulating clinical evidence reveals several limitations of these medications, including delayed pharmacodynamics and low remission rates. Therefore, it is necessary to search for new drugs and develop effective strategies for depression treatment. Bezafibrate (BEZ), which can activate proliferator-activated receptor a (PPARα), exhibit various biological functions, such as improving mitochondrial function, reducing neuroinflammation, and improving cognitive function. This study is to explore whether BEZ has antidepressant-like effects and its potential mechanisms. Methods: The antidepressant effects and potential mechanisms of BEZ were assessed by using forced swim test, tail suspension test, sucrose preference test, western blot, gene interference, and immunofluorescence in the chronic unpredictable mild stress (CUMS) models of depression. Results: Results showed that BEZ treatment significantly reversed depressive behavior in CUMS mice. The administration of BEZ obviously promoted the expression of PPAR, enhanced the BDNF signaling pathway, promoted hippocampal neurogenesis in CUMS mice. In addition, the pharmacologcial inhibitors GW6471 and K252a were obviously prevented the antidepressant effect of BEZ. Furthermore, gene knockdown of hippocampal PPARα or BDNF by using AAV-PPARα-shRNA-EGFP and AAV-BDNF-shRNA-EGFP, can remarkably inhibit the antidepressant effect of BEZ. Conclusion: Collectively, the behavioral and neurobiological results demonstrate that BEZ exhibits antidepressant-like activity through PPARα/BDNF signaling pathway and may use as a potential antidepressant.
Keywords: Bezafibrate, Depression, PPARα, BNDF, CUMS
Received: 17 Mar 2025; Accepted: 21 Apr 2025.
Copyright: © 2025 Xu, Zhou, Zhou, Wang, Wang, Jiang and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Bo Jiang, Department of Neurosurgery, Second Affiliated Hospital of Nantong University, Nantong, China
Wei Zhao, Department of Pharmacology, Pharmacy College, Nantong University, Nantong, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.