{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T05:26:37Z","timestamp":1794288397071,"version":"4.9.0"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T00:00:00Z","timestamp":1583366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NO.81471223"],"award-info":[{"award-number":["NO.81471223"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Project of Enhancing School with Innovation of Guangdong Ocean University","award":["GDOU2013050110"],"award-info":[{"award-number":["GDOU2013050110"]}]},{"name":"Guangdong Provincial Science and Technology Planning Project of Guangdong Province, China","award":["2016A020215153"],"award-info":[{"award-number":["2016A020215153"]}]},{"name":"Guangdong Provincial Science and Technology Planning Project of Guangdong Province, China","award":["2016B020235001"],"award-info":[{"award-number":["2016B020235001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Clinical evidence indicated that eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) in depression treatment. However, possible mechanisms remain unclear. Here, a chronic unpredictable mild stress (CUMS)-induced model of depression was used to compare EPA and DHA anti-depressant effects. After EPA or DHA feeding, depression-like behavior, brain n-3\/n-6 PUFAs profile, serum corticosterone and cholesterol concentration, hippocampal neurotransmitters, microglial and astrocyte related function, as well as neuronal apoptosis and survival signaling pathways were studied. EPA was more effective than DHA to ameliorate CUMS-induced body weight loss, and depression-like behaviors, such as increasing sucrose preference, shortening immobility time and increasing locomotor activity. CUMS-induced corticosterone elevation was reversed by bother fatty acids, while increased cholesterol was only reduced by EPA supplement. Lower hippocampal noradrenaline and 5-hydroxytryptamine concentrations in CUMS rats were also reversed by both EPA and DHA supplement. However, even though CUMS-induced microglial activation and associated increased IL-1\u03b2 were inhibited by both EPA and DHA supplement, increased IL-6 and TNF-\u03b1 levels were only reduced by EPA. Compared to DHA, EPA could improve CUMS-induced suppressive astrocyte biomarkers and associated BDNF-TrkB signaling. Moreover, EPA was more effective than DHA to attenuate CUMS-induced higher hippocampal NGF, GDNF, NF-\u03baB, p38, p75, and bax expressions, but reversed bcl-2 reduction. This study for the first time revealed the mechanisms by which EPA was more powerful than DHA in anti-inflammation, normalizing astrocyte and neurotrophin function and regulating NF-\u03baB, p38 and apoptosis signaling. These findings reveal the different mechanisms of EPA and DHA in clinical depression treatment.<\/jats:p>","DOI":"10.3390\/ijms21051769","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T07:33:46Z","timestamp":1583480026000},"page":"1769","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":142,"title":["EPA is More Effective than DHA to Improve Depression-Like Behavior, Glia Cell Dysfunction and Hippcampal Apoptosis Signaling in a Chronic Stress-Induced Rat Model of Depression"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4748-8675","authenticated-orcid":false,"given":"Zhilan","family":"Peng","sequence":"first","affiliation":[{"name":"Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"},{"name":"Shenzhen Institutes of Guangdong Ocean University, Shenzhen 518120, China"},{"name":"Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4349-5918","authenticated-orcid":false,"given":"Cai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"},{"name":"Shenzhen Institutes of Guangdong Ocean University, Shenzhen 518120, China"},{"name":"Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Yan","sequence":"additional","affiliation":[{"name":"Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8667-860X","authenticated-orcid":false,"given":"Yongping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"},{"name":"Shenzhen Institutes of Guangdong Ocean University, Shenzhen 518120, China"},{"name":"Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6551-684X","authenticated-orcid":false,"given":"Zhiyou","family":"Yang","sequence":"additional","affiliation":[{"name":"Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"},{"name":"Shenzhen Institutes of Guangdong Ocean University, Shenzhen 518120, China"},{"name":"Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai","family":"Song","sequence":"additional","affiliation":[{"name":"Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"},{"name":"Shenzhen Institutes of Guangdong Ocean University, Shenzhen 518120, China"},{"name":"Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1177\/1073858410371379","article-title":"Inflammation in neurological disorders: A help or a hindrance?","volume":"16","year":"2010","journal-title":"Neuroscientist"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jneuroim.2010.09.020","article-title":"Inflammation and gliosis in neurological diseases\u2014Clinical implications","volume":"231","author":"Czlonkowska","year":"2011","journal-title":"J. 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