Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway
Yanqin Wu, Fusheng Sun, Yujin Guo, Yumao Zhang, Li Li, Ruili Dang, Pei Jiang
Abstract
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, <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mtext>CUMS</a:mtext> <a:mo>+</a:mo> <a:mtext>CUR</a:mtext> </a:math> , and <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mtext>CUMS</c:mtext> <c:mo>+</c:mo> <c:mtext>CUR</c:mtext> <c:mo>+</c:mo> <c:mtext>SR</c:mtext> <c:mn>18292</c:mn> </c:math> (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.