The hypothalamus as the primary brain region of metabolic abnormalities in APP/PS1 transgenic mouse model of Alzheimer's disease

doi:10.1016/j.bbadis.2017.10.028

科研成果详情

题名	The hypothalamus as the primary brain region of metabolic abnormalities in APP/PS1 transgenic mouse model of Alzheimer's disease
作者	Zheng, Hong1; Zhou, Qi 1; Du, Yao 1; Li, Chen 1; Xu, Pengtao 1; Lin, Li2; Xiao, Jian2; Gao, Hongchang1
发表日期	2018-01
发表期刊	BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Brain region Cognition Metabolism Early-diagnosis Neurotransmitter
其他关键词	ENERGY-METABOLISM ; A-BETA ; CELL-DEATH ; DYSFUNCTION ; MICE ; EXPRESSION ; TRANSPORT ; DEMENTIA ; DECLINE ; EVENTS
摘要	Alzheimer's disease (AD) is an amyloid-related neurodegenerative disorder and is also considered to be a metabolic disease. Thus, investigation of metabolic mechanisms of amyloid pathology progression is of substantial importance for the diagnosis, prevention and treatment of AD. In the present study, cognitive function and brain metabolism were explored in the transgenic APP/PS1 mouse model of amyloid pathology at different ages. Using an NMR-based metabolomic approach, we examined metabolic changes in six different brain regions of wild-type and APP/PS1 mice at 1, 5 and 10 months of age. Learning and memory performance in mice was evaluated using the Morris water maze test. Furthermore, a generalized linear mixed model was employed to analyze the interaction effect between the mouse-type and brain region (or age) on metabolic alterations. Brain region-specific changes in energy metabolism occurred prior to a very early-stage of amyloid pathology (1 month of age) in APP/PS1 mice. A hypermetabolic state was identified in the brains of APP/PS1 mice at 5 months of age, and the hypothalamus was identified as the main brain region that underwent significant metabolic alterations. The cognitive function of APP/PS1 mice was impaired at 10 months of age; moreover, the hypermetabolic state identified in various brain regions at 5 months of age was also significantly decreased. In conclusion, our results suggest that a hypothalamic metabolism abnormality may comprise a potential indicator for the early-diagnosis and monitoring of amyloid pathology progression.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21605115, 21575105]; Public Welfare Technology Application Research Foundation of Zhejiang Province [2017C33066]
出版者	ELSEVIER
出版地	AMSTERDAM
ISSN	0925-4439
EISSN	1879-260X
卷号	1864 期号:1 页码:263-273
DOI	10.1016/j.bbadis.2017.10.028
页数	11
WOS类目	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS记录号	WOS:000418219900024
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	29107091
SCOPUSEID	2-s2.0-85032447156
通讯作者地址	[Gao, Hongchang]Institute of Metabonomics & Medical NMR,School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Molecular Medicine;Molecular Biology
引用统计	被引频次：31[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/1765
专题	药学院（分析测试中心）研究生工作部（研究生院）药学院（分析测试中心）_分子药理研究与教学中心
通讯作者	Gao, Hongchang
作者单位	1.Institute of Metabonomics & Medical NMR,School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,325035,China; 2.Institute of Molecular Pharmacology,School of Pharmaceutical Science,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	Zheng, Hong,Zhou, Qi,Du, Yao,et al. The hypothalamus as the primary brain region of metabolic abnormalities in APP/PS1 transgenic mouse model of Alzheimer's disease[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,2018,1864(1):263-273.
APA	Zheng, Hong., Zhou, Qi., Du, Yao., Li, Chen., Xu, Pengtao., ... & Gao, Hongchang. (2018). The hypothalamus as the primary brain region of metabolic abnormalities in APP/PS1 transgenic mouse model of Alzheimer's disease. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1864(1), 263-273.
MLA	Zheng, Hong,et al."The hypothalamus as the primary brain region of metabolic abnormalities in APP/PS1 transgenic mouse model of Alzheimer's disease".BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 1864.1(2018):263-273.