SIRT1 Mediates Apelin-13 in Ameliorating Chronic Normobaric Hypoxia-induced Anxiety-like Behavior by Suppressing NF-κB Pathway in Mice Hippocampus

doi:10.1016/j.neuroscience.2018.04.013

科研成果详情

题名	SIRT1 Mediates Apelin-13 in Ameliorating Chronic Normobaric Hypoxia-induced Anxiety-like Behavior by Suppressing NF-κB Pathway in Mice Hippocampus
作者	Fan, Junming; Guang, Hui; Zhang, Haizeng; Chen, Danyang; Ding, Lu; Fan, Xiaofang; Xue, Feng; Gan, Zhuohui; Wang, Yongyu; Mao, Sunzhong; Hu, Lianggang; Gong, Yongsheng
发表日期	2018-06-15
发表期刊	Neuroscience 影响因子和分区
语种	英语
原始文献类型	Journal Article ; Research Support, Non-U.S. Gov't
关键词	NF-κB SIRT1 anxiety-like behavior apelin hippocampus hypoxia
其他关键词	DEPRESSIVE-LIKE BEHAVIOR ; INTERMITTENT HYPOXIA ; PULMONARY-HYPERTENSION ; MICROGLIAL ACTIVATION ; ANTIDEPRESSANT-LIKE ; RESVERATROL ; INFLAMMATION ; BRAIN ; MECHANISMS ; SLEEP
摘要	We previously showed that apelin-13 ameliorates chronic normobaric hypoxia (CNH)-induced anxiety-like behavior in mice, the mechanism, however, is not well known. This study aims to investigate whether SIRT1 is involved in the anxiolytic effect of apelin-13 in CNH-treated mice, and to illustrate the potential underlying mechanism. We showed that apelin-13 treatment reversed a decrease in SIRT1 and an increase in acetylated p65 (lysine 310) proteins' expression in hippocampus of CNH-treated mice, indicating that apelin-13 inhibited NF-κB signaling pathway by activating SIRT1. Behaviorally, apelin-13 ameliorated CNH-induced anxiety-like behavior, EX-527 blocked the beneficial effect of apelin-13, and the anxiogenic effect of CNH was attenuated by resveratrol pretreatment, suggesting that SIRT1 was involved in the effect of apelin-13 against CNH-induced anxiety-like behavior in mice. We also showed that resveratrol treatment decreased IL-1β, IL-6, TNF-ɑ, PCNA, Bcl-2, and acetyl-p65 levels, but increased Bax and caspase 3 levels in hippocampus, suggesting a suppressive effect of resveratrol on cellular neuroinflammation and proliferation while a promotive effect on apoptosis of microglia in hippocampus. Finally, blockade of NF-κB activity by PDTC diminished CNH-induced anxiety-like behavior, indicating that NF-κB was involved in CNH-induced anxiety-like behavior in mice. In conclusion, this study provides the first evidence that SIRT1 mediates the anxiolytic effect of apelin-13 in CNH-treated mice through the inhibition of NF-κB pathway. These results imply that dysfunction of the apelin-SIRT1-NF-κB axis in hippocampus represents a potential mechanism that results in the induction of neuroinflammation and reduction in neuroprotection, thus induces anxiety-like behavior in CNH-treated mice.
资助项目	Natural Science Foundation of Zhejiang Province of China [LY16H010006, LY17H010007, LY18H010007, LY14H010005]; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry of China
出版者	PERGAMON-ELSEVIER SCIENCE LTD
ISSN	0306-4522
EISSN	1873-7544
卷号	381 页码:22-34
DOI	10.1016/j.neuroscience.2018.04.013
页数	13
WOS类目	Neurosciences
WOS研究方向	Neurosciences & Neurology
WOS记录号	WOS:000432744500003
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	29680708
SCOPUSEID	2-s2.0-85046167407
通讯作者地址	[Gong, Yongsheng]Institute of Hypoxia Medicine,Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Neuroscience (all)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/186067
专题	温州医科大学
通讯作者	Gong, Yongsheng
作者单位	Institute of Hypoxia Medicine,Wenzhou Medical University,Wenzhou,325035,China
第一作者单位	温州医科大学
通讯作者单位	温州医科大学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Fan, Junming,Guang, Hui,Zhang, Haizeng,et al. SIRT1 Mediates Apelin-13 in Ameliorating Chronic Normobaric Hypoxia-induced Anxiety-like Behavior by Suppressing NF-κB Pathway in Mice Hippocampus[J]. Neuroscience,2018,381:22-34.
APA	Fan, Junming., Guang, Hui., Zhang, Haizeng., Chen, Danyang., Ding, Lu., ... & Gong, Yongsheng. (2018). SIRT1 Mediates Apelin-13 in Ameliorating Chronic Normobaric Hypoxia-induced Anxiety-like Behavior by Suppressing NF-κB Pathway in Mice Hippocampus. Neuroscience, 381, 22-34.
MLA	Fan, Junming,et al."SIRT1 Mediates Apelin-13 in Ameliorating Chronic Normobaric Hypoxia-induced Anxiety-like Behavior by Suppressing NF-κB Pathway in Mice Hippocampus".Neuroscience 381(2018):22-34.