Electronegative very-low-density lipoprotein induces brain inflammation and cognitive dysfunction in mice

Abstract Epidemiologic studies have indicated that dyslipidemia may facilitate the progression of cognitive dysfunction. We previously showed that patients with metabolic syndrome (MetS) had significantly higher plasma levels of electronegative very-low-density lipoprotein (VLDL) than did healthy co...

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Autores principales:	Ying-Shao Lin, Ching-Kuan Liu, Hsiang-Chun Lee, Mei-Chuan Chou, Liang-Yin Ke, Chu-Huang Chen, Shiou-Lan Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/64f3ac79b07b49e49aa56ea7fbf697e8
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spelling	oai:doaj.org-article:64f3ac79b07b49e49aa56ea7fbf697e82021-12-02T16:31:13ZElectronegative very-low-density lipoprotein induces brain inflammation and cognitive dysfunction in mice10.1038/s41598-021-85502-02045-2322https://doaj.org/article/64f3ac79b07b49e49aa56ea7fbf697e82021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85502-0https://doaj.org/toc/2045-2322Abstract Epidemiologic studies have indicated that dyslipidemia may facilitate the progression of cognitive dysfunction. We previously showed that patients with metabolic syndrome (MetS) had significantly higher plasma levels of electronegative very-low-density lipoprotein (VLDL) than did healthy controls. However, the effects of electronegative-VLDL on the brain and cognitive function remain unclear. In this study, VLDL isolated from healthy volunteers (nVLDL) or patients with MetS (metVLDL) was administered to mice by means of tail vein injection. Cognitive function was assessed by using the Y maze test, and plasma and brain tissues were analyzed. We found that mice injected with metVLDL but not nVLDL exhibited significant hippocampus CA3 neuronal cell loss and cognitive dysfunction. In mice injected with nVLDL, we observed mild glial cell activation in the medial prefrontal cortex (mPFC) and hippocampus CA3. However, in mice injected with metVLDL, plasma and brain TNF-α and Aβ-42 levels and glial cell activation in the mPFC and whole hippocampus were higher than those in control mice. In conclusion, long-term exposure to metVLDL induced levels of TNF-α, Aβ-42, and glial cells in the brain, contributing to the progression of cognitive dysfunction. Our findings suggest that electronegative-VLDL levels may represent a new therapeutic target for cognitive dysfunction.Ying-Shao LinChing-Kuan LiuHsiang-Chun LeeMei-Chuan ChouLiang-Yin KeChu-Huang ChenShiou-Lan ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ying-Shao Lin Ching-Kuan Liu Hsiang-Chun Lee Mei-Chuan Chou Liang-Yin Ke Chu-Huang Chen Shiou-Lan Chen Electronegative very-low-density lipoprotein induces brain inflammation and cognitive dysfunction in mice
description	Abstract Epidemiologic studies have indicated that dyslipidemia may facilitate the progression of cognitive dysfunction. We previously showed that patients with metabolic syndrome (MetS) had significantly higher plasma levels of electronegative very-low-density lipoprotein (VLDL) than did healthy controls. However, the effects of electronegative-VLDL on the brain and cognitive function remain unclear. In this study, VLDL isolated from healthy volunteers (nVLDL) or patients with MetS (metVLDL) was administered to mice by means of tail vein injection. Cognitive function was assessed by using the Y maze test, and plasma and brain tissues were analyzed. We found that mice injected with metVLDL but not nVLDL exhibited significant hippocampus CA3 neuronal cell loss and cognitive dysfunction. In mice injected with nVLDL, we observed mild glial cell activation in the medial prefrontal cortex (mPFC) and hippocampus CA3. However, in mice injected with metVLDL, plasma and brain TNF-α and Aβ-42 levels and glial cell activation in the mPFC and whole hippocampus were higher than those in control mice. In conclusion, long-term exposure to metVLDL induced levels of TNF-α, Aβ-42, and glial cells in the brain, contributing to the progression of cognitive dysfunction. Our findings suggest that electronegative-VLDL levels may represent a new therapeutic target for cognitive dysfunction.
format	article
author	Ying-Shao Lin Ching-Kuan Liu Hsiang-Chun Lee Mei-Chuan Chou Liang-Yin Ke Chu-Huang Chen Shiou-Lan Chen
author_facet	Ying-Shao Lin Ching-Kuan Liu Hsiang-Chun Lee Mei-Chuan Chou Liang-Yin Ke Chu-Huang Chen Shiou-Lan Chen
author_sort	Ying-Shao Lin
title	Electronegative very-low-density lipoprotein induces brain inflammation and cognitive dysfunction in mice
title_short	Electronegative very-low-density lipoprotein induces brain inflammation and cognitive dysfunction in mice
title_full	Electronegative very-low-density lipoprotein induces brain inflammation and cognitive dysfunction in mice
title_fullStr	Electronegative very-low-density lipoprotein induces brain inflammation and cognitive dysfunction in mice
title_full_unstemmed	Electronegative very-low-density lipoprotein induces brain inflammation and cognitive dysfunction in mice
title_sort	electronegative very-low-density lipoprotein induces brain inflammation and cognitive dysfunction in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/64f3ac79b07b49e49aa56ea7fbf697e8
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Electronegative very-low-density lipoprotein induces brain inflammation and cognitive dysfunction in mice

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