{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T23:57:15Z","timestamp":1784159835833,"version":"3.55.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:00:00Z","timestamp":1756512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Scientific Research Project of Jiangsu Province","award":["BRA2020204"],"award-info":[{"award-number":["BRA2020204"]}]},{"DOI":"10.13039\/100017962","name":"Jiangsu Provincial Health Commission","doi-asserted-by":"publisher","award":["K2024072"],"award-info":[{"award-number":["K2024072"]}],"id":[{"id":"10.13039\/100017962","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Project of Nantong Health Commission","award":["MS2024025"],"award-info":[{"award-number":["MS2024025"]}]},{"name":"Research Project of Nantong Health Commission","award":["MSZ2023026"],"award-info":[{"award-number":["MSZ2023026"]}]},{"name":"Research Project of Nantong Health Commission","award":["MS2023041"],"award-info":[{"award-number":["MS2023041"]}]},{"name":"Research Project of Nantong Health Commission","award":["MS2023049"],"award-info":[{"award-number":["MS2023049"]}]},{"name":"Key Medical Talents Financial Assistance of Nantong"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>It is well established that peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1) plays a crucial role in the pathogenesis of depression. Several PPAR\u03b1 agonists, including WY14643, fenofibrate, and gemfibrozil, have been reported to produce antidepressant-like effects in mouse models through PPAR\u03b1-mediated enhancement of hippocampal brain-derived neurotrophic factor (BDNF) signaling and neurogenesis. Pemafibrate is a novel and highly selective modulator of PPAR\u03b1; we therefore hypothesized that it might also exhibit antidepressant-like efficacy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We employed 2 established mouse models of depression, chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS), to evaluate the potential antidepressant effects of pemafibrate. Western blotting and immunofluorescence were used to assess whether pemafibrate treatment counteracts chronic stress-induced suppression of hippocampal PPAR\u03b1, BDNF signaling, and neurogenesis. To investigate the mechanism of action, we utilized pharmacological inhibitors (GW6471 for PPAR\u03b1 and K252a for BDNF signaling) combined with adeno-associated virus\u2013mediated genetic knockdown approaches.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Repeated pemafibrate administration significantly ameliorated chronic stress-induced depressive-like behaviors and restored hippocampal PPAR\u03b1 levels, BDNF signaling, and neurogenesis in both models. These antidepressant effects were markedly attenuated by co-administration of GW6471 or K252a. Similarly, genetic knockdown of either hippocampal PPAR\u03b1 or BDNF abolished pemafibrate\u2019s antidepressant-like actions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Pemafibrate exerts antidepressant-like effects in both CUMS and CRS mouse models by promoting hippocampal PPAR\u03b1 and BDNF signaling.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ijnp\/pyaf063","type":"journal-article","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T13:09:27Z","timestamp":1756559367000},"source":"Crossref","is-referenced-by-count":1,"title":["Pemafibrate treatment produces antidepressant-like effects in CUMS and CRS models through activation of hippocampal PPAR\u03b1 and BDNF signaling"],"prefix":"10.1093","volume":"28","author":[{"given":"Jin","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Affiliated Hospital 2 of Nantong University , Nantong 226000, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Affiliated Hospital 2 of Nantong University , Nantong 226000, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Fan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology , Luoyang 471003, Henan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Yi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Affiliated Hospital 2 of Nantong University , Nantong 226000, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Affiliated Hospital 2 of Nantong University , Nantong 226000, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nantong Hospital of Traditional Chinese Medicine , Nantong 226009, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Nantong University , Nantong 226001, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Affiliated Hospital 2 of Nantong University , Nantong 226000, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Ming","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Affiliated Hospital 2 of Nantong University , Nantong 226000, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1577-7272","authenticated-orcid":false,"given":"Da-Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Affiliated Hospital 2 of Nantong University , Nantong 226000, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,30]]},"reference":[{"key":"2025092211111915200_ref1","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1177\/070674371405900306","article-title":"The mistreatment of major depressive disorder","volume":"59","author":"Paris","year":"2014","journal-title":"Can J 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