{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T15:58:48Z","timestamp":1780934328600,"version":"3.54.1"},"reference-count":32,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T00:00:00Z","timestamp":1635552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1G1A1013523"],"award-info":[{"award-number":["NRF-2021R1G1A1013523"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007631","name":"Chungnam National University Hospital","doi-asserted-by":"publisher","award":["2019 (to Y.R.H.)"],"award-info":[{"award-number":["2019 (to Y.R.H.)"]}],"id":[{"id":"10.13039\/501100007631","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although the cause of neurological disease in patients with chronic kidney disease (CKD) has not been completely identified yet, recent papers have identified accumulated uremic toxin as its main cause. Additionally, omega-3 polyunsaturated fatty acid (\u03c9-3 PUFA) plays an important role in maintaining normal nerve function, but its protective effects against uremic toxin is unclear. The objective of this study was to identify brain damage caused by uremic toxicity and determine the protective effects of \u03c9-3 PUFA against uremic toxin. We divided mice into the following groups: wild-type (wt) sham (n = 8), \u03c9-3 PUFA sham (n = 8), Fat-1 sham (n = 8), ischemia-reperfusion (IR) (n = 20), and \u03c9-3 PUFA+IR (n = 20) Fat-1+IR (n = 20). Brain tissue, kidney tissue, and blood were collected three days after the operation of mice (sham and IR operation). This study showed that Ki67 and neuronal nuclei (NeuN) decreased in the brain of uremic mice as compared to wt mice brain, but increased in the \u03c9-3 PUFA-treated uremic mice and the brain of uremic Fat-1 mice as compared to the brain of uremic mice. The pro-apoptotic protein expressions were increased, whereas anti-apoptotic protein expression decreased in the brain of uremic mice as compared to wt mice brain. However, apoptotic protein expression decreased in the \u03c9-3 PUFA-treated uremic mice and the brain of uremic Fat-1 mice as compared to the brain of uremic mice. Furthermore, the brain of \u03c9-3 PUFA-treated uremic mice and uremic Fat-1 mice showed increased expression of p-PI3K, p-PDK1, and p-Akt as compared to the brain of uremic mice. We confirm that uremic toxin damages the brain and causes cell death. In these injuries, \u03c9-3 PUFA plays an important role in neuroprotection through PI(3)K-Akt signaling.<\/jats:p>","DOI":"10.3390\/ijms222111802","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:21:34Z","timestamp":1635805294000},"page":"11802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Omega-3 Polyunsaturated Fatty Acid Attenuates Uremia-Induced Brain Damage in Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Eun-Ji","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Medical Science, Medical School, Chungnam National University, Daejeon 35015, Korea"},{"name":"Department of Nephrology, Medical School, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9140-6900","authenticated-orcid":false,"given":"Young Rok","family":"Ham","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Medical School, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Ah","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Medical School, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Young","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Medical School, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Ryang","family":"Na","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Medical School, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang Wook","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Medical School, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jwa-Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Medical School, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2870-3958","authenticated-orcid":false,"given":"Dae Eun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Medical School, Chungnam National University, Daejeon 35015, Korea"},{"name":"Department of Nephrology, Medical School, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3390\/toxins6020665","article-title":"Protein-bound uremic toxins: New culprits of cardiovascular events in chronic kidney disease patients","volume":"6","author":"Ito","year":"2014","journal-title":"Toxins"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1053\/j.ajkd.2018.03.028","article-title":"Distant organ dysfunction in acute kidney injury: A review","volume":"72","author":"Lee","year":"2018","journal-title":"Am. 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Urol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11802\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:23:33Z","timestamp":1760167413000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11802"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,30]]},"references-count":32,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222111802"],"URL":"https:\/\/doi.org\/10.3390\/ijms222111802","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,30]]}}}