Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway
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 invest...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Behavioural Neurology |
| Online Access: | http://dx.doi.org/10.1155/2021/2630445 |
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| author | Yanqin Wu Fusheng Sun Yujin Guo Yumao Zhang Li Li Ruili Dang Pei Jiang |
| author_facet | Yanqin Wu Fusheng Sun Yujin Guo Yumao Zhang Li Li Ruili Dang Pei Jiang |
| author_sort | Yanqin Wu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3a7e6688cb1f4eac9e44893712343132 |
| institution | Kabale University |
| issn | 1875-8584 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Behavioural Neurology |
| spelling | doaj-art-3a7e6688cb1f4eac9e448937123431322025-02-03T07:24:15ZengWileyBehavioural Neurology1875-85842021-01-01202110.1155/2021/2630445Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF PathwayYanqin Wu0Fusheng Sun1Yujin Guo2Yumao Zhang3Li Li4Ruili Dang5Pei Jiang6Department of PharmacyDepartment of PharmacyInstitute of Clinical PharmacyDepartment of PharmacyDepartment of PharmacyInstitute of Clinical PharmacyInstitute of Clinical PharmacyBackground 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.http://dx.doi.org/10.1155/2021/2630445 |
| spellingShingle | Yanqin Wu Fusheng Sun Yujin Guo Yumao Zhang Li Li Ruili Dang Pei Jiang Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway Behavioural Neurology |
| title | Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway |
| title_full | Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway |
| title_fullStr | Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway |
| title_full_unstemmed | Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway |
| title_short | Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway |
| title_sort | curcumin relieves chronic unpredictable mild stress induced depression like behavior through the pgc 1α fndc5 bdnf pathway |
| url | http://dx.doi.org/10.1155/2021/2630445 |
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