Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway

• Published in: Behavioural neurology Vol. 2021; pp. 2630445 - 13
• Main Authors: Wu, Yanqin, Sun, Fusheng, Guo, Yujin, Zhang, Yumao, Li, Li, Dang, Ruili, Jiang, Pei
• Format: Journal Article
• Language: English
• Published: Netherlands Hindawi 14.12.2021; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Analysis; Animals; Antidepressants; Behavior; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Clinical trials; Curcumin - pharmacology; Depression - drug therapy; Depression, Mental; Disease Models, Animal; Fibronectins - metabolism; Gene expression; Health aspects; Hippocampus - metabolism; Laboratory animals; Mental depression; Oxidative stress; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; Rats; Signal Transduction; Stress, Psychological - drug therapy; Sucrose; China; Beijing China
• ISSN: 0953-4180; 1875-8584
• DOI: 10.1155/2021/2630445

Background and Aim. Increasing evidence suggests that the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)/fibronectin type III domain-containing 5 (FNDC5)/brain-derived neurotrophic factor (BDNF) pathway might be critical for neuroprotection. Our present study is aimed at investigating the antidepressant-like effects of curcumin (CUR) in a chronic unpredictable mild stress- (CUMS-) induced depression rat model and explore whether the PGC-1α/FNDC5/BDNF pathway is the major driving force behind the therapeutic effects of CUR. Methods. All rats were randomly divided into four groups, namely, control, CUMS, CUMS+CUR, and CUMS+CUR+SR18292 (PGC-1α inhibitor). Behavioral tests were conducted to assess the antidepressant-like effects of CUR. The expressions of PGC-1α, estrogen-related receptor alpha (ERRα), FNDC5, and BDNF were determined to investigate the regulatory effects of CUR on the PGC-1α/FNDC5/BDNF pathway. The PGC-1α inhibitor SR18292 was used to explore the role of PGC-1α in the induction of BDNF by CUR. Results. Daily gavage of 100 mg/kg CUR successfully attenuated the abnormal behaviors induced by CUMS and effectively prevented CUMS-induced reduction of PGC-1α, ERRα, FNDC5, and BDNF expressions. CUR also enhanced PGC-1α and ERRα translocation from cytoplasm to nucleus. Furthermore, we found that CUR supplementation effectively promoted neurocyte proliferation and suppressed neuronal apoptosis induced by CUMS. Of note, the PGC-1α inhibitor SR18292 remarkably reversed the beneficial effects of CUR on depressed rats, indicating an important role of PGC-1α in the antidepressant-like effects of CUR. Conclusion. Collectively, our data evaluating the neuroprotective action of CUR in the CUMS rats highlights the involvement of the PGC-1α/FNDC5/BDNF pathway in the antidepressant-like effects of CUR.