Dopamine Burden Triggers Cholesterol Overload Following Disruption of Synaptogenesis in Minimal Hepatic Encephalopathy

doi:10.1016/j.neuroscience.2019.04.056

科研成果详情

题名	Dopamine Burden Triggers Cholesterol Overload Following Disruption of Synaptogenesis in Minimal Hepatic Encephalopathy
作者	Zhuge, Weishan 1; Wen, Fangfang 2; Ni, Zhihui3; Zheng, Zhao 3; Zhu, Xiaohong3; Lin, Jianting 3; Wang, Jian2; Zhuge, Qichuan3; Ding, Saidan2
发表日期	2019-07-01
发表期刊	NEUROSCIENCE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	minimal hepatic encephalopathy dopamine cholesterol PPAR gamma synaptogenesis
其他关键词	METABOLISM ; DISEASE ; NEURODEGENERATION ; ASTROCYTES ; DIAGNOSIS ; RELEASE
摘要	The contribution of Dopamine (DA) to minimal hepatic encephalopathy (MHE) has been demonstrated. However, recent studies have revealed that cholesterol (CHO) treatment substantially increased the risk of dementia. The objectives of this study were to investigate whether CHO was induced by DA overload and its involvement in DA-induced cognitive impairment in MHE. Our study showed that DA treatment triggered CHO biosynthesis via the activation of JNK3/SREBP2 signaling pathway in primary cultured astrocytes. Conditioned media from DA-treated astrocytes increased CHO uptake by primary cultured neurons and disrupted synaptic formations; at the same time, inhibition of CHO synthesis and transportation from astrocytes diminished the disruption of synaptogenesis, which indicates the involvement of CHO in the perturbation of neural synaptogenesis in vitro. Secondary secretion of DA from primary cultured neurons was stimulated by CHO secreted from astrocytes. DA induced synergistic decreases of PPAR gamma/pERK/pCREB expressions in the presence of CHO in neurons, leading to synergistic synaptic impairment. Memory impairments were observed in MHE/DA-treated rats, which were partially rescued by atorvastatin (ATVS) treatment, confirming the involvement of CHO burden in vivo. Overall, our study suggests that DA overload triggers obvious CHO production from astrocytes. Excessive CHO in turn triggered neurons to secrete abundant DA and DA burden in combination with CHO overload elicit the cognitive decline and memory loss via PPAR gamma/ERK/CREB pathway in MHE. (C) 2019 Published by Elsevier Ltd on behalf of IBRO.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81671042, 81300308, 81171088, 81371396]
出版者	PERGAMON-ELSEVIER SCIENCE LTD
出版地	OXFORD
ISSN	0306-4522
EISSN	1873-7544
卷号	410 页码:1-15
DOI	10.1016/j.neuroscience.2019.04.056
页数	15
WOS类目	Neurosciences
WOS研究方向	Neurosciences & Neurology
WOS记录号	WOS:000472607500001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	31078686
SCOPUSEID	2-s2.0-85065820698
通讯作者地址	[Zhuge, Qichuan]Neurosurgery Department,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China
Scopus学科分类	Neuroscience (all)
引用统计	被引频次：4[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/14145
专题	附属第一医院
通讯作者	Zhuge, Qichuan
作者单位	1.Gastrointestinal Surgery,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 2.Zhejiang Provincial Key Laboratory of Aging and Neurological Disease Research,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 3.Neurosurgery Department,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China
第一作者单位	附属第一医院
通讯作者单位	附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Zhuge, Weishan,Wen, Fangfang,Ni, Zhihui,et al. Dopamine Burden Triggers Cholesterol Overload Following Disruption of Synaptogenesis in Minimal Hepatic Encephalopathy[J]. NEUROSCIENCE,2019,410:1-15.
APA	Zhuge, Weishan., Wen, Fangfang., Ni, Zhihui., Zheng, Zhao., Zhu, Xiaohong., ... & Ding, Saidan. (2019). Dopamine Burden Triggers Cholesterol Overload Following Disruption of Synaptogenesis in Minimal Hepatic Encephalopathy. NEUROSCIENCE, 410, 1-15.
MLA	Zhuge, Weishan,et al."Dopamine Burden Triggers Cholesterol Overload Following Disruption of Synaptogenesis in Minimal Hepatic Encephalopathy".NEUROSCIENCE 410(2019):1-15.