β-hydroxybutyrate Alleviates Learning and Memory Impairment Through the SIRT1 Pathway in D-Galactose-Injured Mice

Learning and memory impairment is a common clinical symptom of aging and nervous system injuries, and seriously affects quality of life. Memory impairment is associated with increased oxidative stress (OS) and inflammatory response. β-hydroxybutyrate (BHBA) is a water-soluble endogenous small-molecu...

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Autores principales:	Xiaojing Yang, Ruonan Wang, Hailun Zhou, Li Wang, Rui Wang, Haomin Li, Baodong Tan, Qiong Wu, Xin Xu, Lianxu Cui, Zaiyu Li, Hua Li
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	β-hydroxybutyrate learning and memory impairment oxidative stress NLRP3 SIRT1 FoxO3a Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/07fff407ce95413ea2f01cbcb09be77c
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spelling	oai:doaj.org-article:07fff407ce95413ea2f01cbcb09be77c2021-11-22T05:04:31Zβ-hydroxybutyrate Alleviates Learning and Memory Impairment Through the SIRT1 Pathway in D-Galactose-Injured Mice1663-981210.3389/fphar.2021.751028https://doaj.org/article/07fff407ce95413ea2f01cbcb09be77c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.751028/fullhttps://doaj.org/toc/1663-9812Learning and memory impairment is a common clinical symptom of aging and nervous system injuries, and seriously affects quality of life. Memory impairment is associated with increased oxidative stress (OS) and inflammatory response. β-hydroxybutyrate (BHBA) is a water-soluble endogenous small-molecule ketone body that easily crosses the blood-brain barrier and has shown neuroprotection activities. In this study, we investigated the effects and mechanisms of BHBA on D-galactose (D-gal)-induced memory impairment in mice by in vitro and in vivo experiments. BHBA was administered intragastrically to D-gal-injured C57BL/6 mice for 42 days. Water maze performance, the morphology of the hippocampus with Nissl staining, the ACh content, OS, and inflammation status were examined. To further investigate the mechanism, hippocampal neuronal cells (HT22) were treated with BHBA with or without the SIRT1 inhibitor or small interfering RNAs against sirt1 (si-SIRT1) before incubation with D-gal. BHBA significantly improved water maze performance; increased the ACh content, SOD activity, and SIRT1 expression; and decreased AChE and LDH activity, ROS, MDA, IL-1β, TNF-α contents, and NLRP3 expression. Further studies with the SIRT inhibitor or siRNAs against sirt1 reversed the above effects of BHBA. Collectively, BHBA inhibited hippocampal OS and the inflammation process to alleviate learning and memory impairment through activating the SIRT1 pathway in D-gal-injured mice, suggesting that BHBA could be a potential option for drug development of learning and memory impairment induced by nervous system injuries.Xiaojing YangXiaojing YangRuonan WangHailun ZhouLi WangRui WangHaomin LiBaodong TanQiong WuXin XuLianxu CuiZaiyu LiHua LiHua LiFrontiers Media S.A.articleβ-hydroxybutyratelearning and memory impairmentoxidative stressNLRP3SIRT1FoxO3aTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	β-hydroxybutyrate learning and memory impairment oxidative stress NLRP3 SIRT1 FoxO3a Therapeutics. Pharmacology RM1-950
spellingShingle	β-hydroxybutyrate learning and memory impairment oxidative stress NLRP3 SIRT1 FoxO3a Therapeutics. Pharmacology RM1-950 Xiaojing Yang Xiaojing Yang Ruonan Wang Hailun Zhou Li Wang Rui Wang Haomin Li Baodong Tan Qiong Wu Xin Xu Lianxu Cui Zaiyu Li Hua Li Hua Li β-hydroxybutyrate Alleviates Learning and Memory Impairment Through the SIRT1 Pathway in D-Galactose-Injured Mice
description	Learning and memory impairment is a common clinical symptom of aging and nervous system injuries, and seriously affects quality of life. Memory impairment is associated with increased oxidative stress (OS) and inflammatory response. β-hydroxybutyrate (BHBA) is a water-soluble endogenous small-molecule ketone body that easily crosses the blood-brain barrier and has shown neuroprotection activities. In this study, we investigated the effects and mechanisms of BHBA on D-galactose (D-gal)-induced memory impairment in mice by in vitro and in vivo experiments. BHBA was administered intragastrically to D-gal-injured C57BL/6 mice for 42 days. Water maze performance, the morphology of the hippocampus with Nissl staining, the ACh content, OS, and inflammation status were examined. To further investigate the mechanism, hippocampal neuronal cells (HT22) were treated with BHBA with or without the SIRT1 inhibitor or small interfering RNAs against sirt1 (si-SIRT1) before incubation with D-gal. BHBA significantly improved water maze performance; increased the ACh content, SOD activity, and SIRT1 expression; and decreased AChE and LDH activity, ROS, MDA, IL-1β, TNF-α contents, and NLRP3 expression. Further studies with the SIRT inhibitor or siRNAs against sirt1 reversed the above effects of BHBA. Collectively, BHBA inhibited hippocampal OS and the inflammation process to alleviate learning and memory impairment through activating the SIRT1 pathway in D-gal-injured mice, suggesting that BHBA could be a potential option for drug development of learning and memory impairment induced by nervous system injuries.
format	article
author	Xiaojing Yang Xiaojing Yang Ruonan Wang Hailun Zhou Li Wang Rui Wang Haomin Li Baodong Tan Qiong Wu Xin Xu Lianxu Cui Zaiyu Li Hua Li Hua Li
author_facet	Xiaojing Yang Xiaojing Yang Ruonan Wang Hailun Zhou Li Wang Rui Wang Haomin Li Baodong Tan Qiong Wu Xin Xu Lianxu Cui Zaiyu Li Hua Li Hua Li
author_sort	Xiaojing Yang
title	β-hydroxybutyrate Alleviates Learning and Memory Impairment Through the SIRT1 Pathway in D-Galactose-Injured Mice
title_short	β-hydroxybutyrate Alleviates Learning and Memory Impairment Through the SIRT1 Pathway in D-Galactose-Injured Mice
title_full	β-hydroxybutyrate Alleviates Learning and Memory Impairment Through the SIRT1 Pathway in D-Galactose-Injured Mice
title_fullStr	β-hydroxybutyrate Alleviates Learning and Memory Impairment Through the SIRT1 Pathway in D-Galactose-Injured Mice
title_full_unstemmed	β-hydroxybutyrate Alleviates Learning and Memory Impairment Through the SIRT1 Pathway in D-Galactose-Injured Mice
title_sort	β-hydroxybutyrate alleviates learning and memory impairment through the sirt1 pathway in d-galactose-injured mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/07fff407ce95413ea2f01cbcb09be77c
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β-hydroxybutyrate Alleviates Learning and Memory Impairment Through the SIRT1 Pathway in D-Galactose-Injured Mice

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