{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T22:44:11Z","timestamp":1794091451965,"version":"4.8.0"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T00:00:00Z","timestamp":1639440000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2020MH375"],"award-info":[{"award-number":["ZR2020MH375"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["2019SMNS012"],"award-info":[{"award-number":["2019SMNS012"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["2019-0747"],"award-info":[{"award-number":["2019-0747"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Research and Development Program of Jining Science and Technology","award":["ZR2020MH375"],"award-info":[{"award-number":["ZR2020MH375"]}]},{"name":"Key Research and Development Program of Jining Science and Technology","award":["2019SMNS012"],"award-info":[{"award-number":["2019SMNS012"]}]},{"name":"Key Research and Development Program of Jining Science and Technology","award":["2019-0747"],"award-info":[{"award-number":["2019-0747"]}]},{"name":"Traditional Chinese Medicine Science and Technology Development Plan of Shandong Province","award":["ZR2020MH375"],"award-info":[{"award-number":["ZR2020MH375"]}]},{"name":"Traditional Chinese Medicine Science and Technology Development Plan of Shandong Province","award":["2019SMNS012"],"award-info":[{"award-number":["2019SMNS012"]}]},{"name":"Traditional Chinese Medicine Science and Technology Development Plan of Shandong Province","award":["2019-0747"],"award-info":[{"award-number":["2019-0747"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Behavioural Neurology"],"published-print":{"date-parts":[[2021,12,14]]},"abstract":"<jats:p>Background and Aim. Increasing evidence suggests that the peroxisome proliferator-activated receptor \u03b3 coactivator 1\u03b1 (PGC-1\u03b1)\/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-1\u03b1\/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, <jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mtext>CUMS<\/a:mtext>\n                        <a:mo>+<\/a:mo>\n                        <a:mtext>CUR<\/a:mtext>\n                     <\/a:math>\n                  <\/jats:inline-formula>, and <jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mtext>CUMS<\/c:mtext>\n                        <c:mo>+<\/c:mo>\n                        <c:mtext>CUR<\/c:mtext>\n                        <c:mo>+<\/c:mo>\n                        <c:mtext>SR<\/c:mtext>\n                        <c:mn>18292<\/c:mn>\n                     <\/c:math>\n                  <\/jats:inline-formula> (PGC-1\u03b1 inhibitor). Behavioral tests were conducted to assess the antidepressant-like effects of CUR. The expressions of PGC-1\u03b1, estrogen-related receptor alpha (ERR\u03b1), FNDC5, and BDNF were determined to investigate the regulatory effects of CUR on the PGC-1\u03b1\/FNDC5\/BDNF pathway. The PGC-1\u03b1 inhibitor SR18292 was used to explore the role of PGC-1\u03b1 in the induction of BDNF by CUR. Results. Daily gavage of 100\u2009mg\/kg CUR successfully attenuated the abnormal behaviors induced by CUMS and effectively prevented CUMS-induced reduction of PGC-1\u03b1, ERR\u03b1, FNDC5, and BDNF expressions. CUR also enhanced PGC-1\u03b1 and ERR\u03b1 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-1\u03b1 inhibitor SR18292 remarkably reversed the beneficial effects of CUR on depressed rats, indicating an important role of PGC-1\u03b1 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-1\u03b1\/FNDC5\/BDNF pathway in the antidepressant-like effects of CUR.<\/jats:p>","DOI":"10.1155\/2021\/2630445","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T21:20:07Z","timestamp":1639516807000},"page":"1-13","source":"Crossref","is-referenced-by-count":34,"title":["Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1\u03b1\/FNDC5\/BDNF Pathway"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8356-9689","authenticated-orcid":true,"given":"Yanqin","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518000 Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fusheng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Qingdao Municipal Hospital, Qingdao, 266005 Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujin","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacy, Jining First People\u2019s Hospital, Jining Medical University, Jining, 272000 Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8027-5431","authenticated-orcid":true,"given":"Yumao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518000 Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3735-3136","authenticated-orcid":true,"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518000 Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8323-8975","authenticated-orcid":true,"given":"Ruili","family":"Dang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacy, Jining First People\u2019s Hospital, Jining Medical University, Jining, 272000 Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8360-7427","authenticated-orcid":true,"given":"Pei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacy, Jining First People\u2019s Hospital, Jining Medical University, Jining, 272000 Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"issue":"10159","key":"1","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the global burden of disease study 2017","volume":"392","author":"C. J. L. Murray","year":"2018","journal-title":"The Lancet"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.14720"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2018.03.014"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1124\/pr.111.005108"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.10.034"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1038\/nature06613"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.05.004"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00065"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1080\/1028415X.2019.1581460"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.09.008"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-018-8500-3"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.3233\/BPL-150019"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2019.02.007"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-015-8370-x"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.12.012"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/9268083"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2020.113002"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.06.002"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5524"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2016.12.071"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2019.1653260"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.12.158"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2013-0133"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.10.049"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2011.02.030"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1007\/BF00187257"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(96)00305-8"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2005.02.007"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-005-0093-5"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1007\/BF00181937"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-002-1_6"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1345-8"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(84)80049-0"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-016-0236-1"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050456"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2014.11.054"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-015-0778-1"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2018.09.028"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145713001661"},{"key":"40","first-page":"93","article-title":"The role of FNDC5\/Irisin in the nervous system and as a mediator for beneficial effects of exercise on the brain","volume-title":"Hormones, Metabolism and the Benefits of Exercise","author":"M. R. Islam","year":"2018"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1002\/9780470985571.ch2"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.22.7947-7956.2003"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308686101"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/537265"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2270-4"},{"key":"46","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2013.155"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.1097\/YPG.0000000000000237"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-847272\/v1"}],"container-title":["Behavioural Neurology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/bn\/2021\/2630445.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bn\/2021\/2630445.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bn\/2021\/2630445.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T21:20:18Z","timestamp":1639516818000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/bn\/2021\/2630445\/"}},"subtitle":[],"editor":[{"given":"Enzo","family":"Emanuele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,12,14]]},"references-count":48,"alternative-id":["2630445","2630445"],"URL":"https:\/\/doi.org\/10.1155\/2021\/2630445","relation":{},"ISSN":["1875-8584","0953-4180"],"issn-type":[{"value":"1875-8584","type":"electronic"},{"value":"0953-4180","type":"print"}],"subject":[],"published":{"date-parts":[[2021,12,14]]}}}