Omega-3 Polyunsaturated Fatty Acid Attenuates Uremia-Induced Brain Damage in Mice

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 (ω-3 PUFA) plays an important role in maintainin...

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Autores principales:	Eun-Ji Kim, Young Rok Ham, Jin Ah Shin, Jin Young Jeong, Ki Ryang Na, Kang Wook Lee, Jwa-Jin Kim, Dae Eun Choi
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ω3-PUFA ischemia-reperfusion uremic toxin indoxyl sulfate brain injury apoptosis Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/c7a431c6d5a941db86d0fa6e2f4e83fd
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spelling	oai:doaj.org-article:c7a431c6d5a941db86d0fa6e2f4e83fd2021-11-11T17:14:48ZOmega-3 Polyunsaturated Fatty Acid Attenuates Uremia-Induced Brain Damage in Mice10.3390/ijms2221118021422-00671661-6596https://doaj.org/article/c7a431c6d5a941db86d0fa6e2f4e83fd2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11802https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Although 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 (ω-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 ω-3 PUFA against uremic toxin. We divided mice into the following groups: wild-type (wt) sham (<i>n</i> = 8), ω-3 PUFA sham (<i>n</i> = 8), Fat-1 sham (<i>n</i> = 8), ischemia-reperfusion (IR) (<i>n</i> = 20), and ω-3 PUFA+IR (<i>n</i> = 20) Fat-1+IR (<i>n</i> = 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 ω-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 ω-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 ω-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, ω-3 PUFA plays an important role in neuroprotection through PI(3)K-Akt signaling.Eun-Ji KimYoung Rok HamJin Ah ShinJin Young JeongKi Ryang NaKang Wook LeeJwa-Jin KimDae Eun ChoiMDPI AGarticleω3-PUFAischemia-reperfusionuremic toxinindoxyl sulfatebrain injuryapoptosisBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11802, p 11802 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ω3-PUFA ischemia-reperfusion uremic toxin indoxyl sulfate brain injury apoptosis Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	ω3-PUFA ischemia-reperfusion uremic toxin indoxyl sulfate brain injury apoptosis Biology (General) QH301-705.5 Chemistry QD1-999 Eun-Ji Kim Young Rok Ham Jin Ah Shin Jin Young Jeong Ki Ryang Na Kang Wook Lee Jwa-Jin Kim Dae Eun Choi Omega-3 Polyunsaturated Fatty Acid Attenuates Uremia-Induced Brain Damage in Mice
description	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 (ω-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 ω-3 PUFA against uremic toxin. We divided mice into the following groups: wild-type (wt) sham (<i>n</i> = 8), ω-3 PUFA sham (<i>n</i> = 8), Fat-1 sham (<i>n</i> = 8), ischemia-reperfusion (IR) (<i>n</i> = 20), and ω-3 PUFA+IR (<i>n</i> = 20) Fat-1+IR (<i>n</i> = 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 ω-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 ω-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 ω-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, ω-3 PUFA plays an important role in neuroprotection through PI(3)K-Akt signaling.
format	article
author	Eun-Ji Kim Young Rok Ham Jin Ah Shin Jin Young Jeong Ki Ryang Na Kang Wook Lee Jwa-Jin Kim Dae Eun Choi
author_facet	Eun-Ji Kim Young Rok Ham Jin Ah Shin Jin Young Jeong Ki Ryang Na Kang Wook Lee Jwa-Jin Kim Dae Eun Choi
author_sort	Eun-Ji Kim
title	Omega-3 Polyunsaturated Fatty Acid Attenuates Uremia-Induced Brain Damage in Mice
title_short	Omega-3 Polyunsaturated Fatty Acid Attenuates Uremia-Induced Brain Damage in Mice
title_full	Omega-3 Polyunsaturated Fatty Acid Attenuates Uremia-Induced Brain Damage in Mice
title_fullStr	Omega-3 Polyunsaturated Fatty Acid Attenuates Uremia-Induced Brain Damage in Mice
title_full_unstemmed	Omega-3 Polyunsaturated Fatty Acid Attenuates Uremia-Induced Brain Damage in Mice
title_sort	omega-3 polyunsaturated fatty acid attenuates uremia-induced brain damage in mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c7a431c6d5a941db86d0fa6e2f4e83fd
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Omega-3 Polyunsaturated Fatty Acid Attenuates Uremia-Induced Brain Damage in Mice

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