Resveratrol Rescues Tau-Induced Cognitive Deficits and Neuropathology in a Mouse Model of Tauopathy

doi:10.2174/1567205016666190801153751

	Resveratrol Rescues Tau-Induced Cognitive Deficits and Neuropathology in a Mouse Model of Tauopathy
	Sun, Xiao-Ying 1,3; Dong, Quan-Xiu 1,3; Zhu, Jie ; Sun, Xun 1,3; Zhang, Li-Fan 3; Qiu, Mandy 2; Yu, Xiao-Lin 3; Liu, Rui-Tian 3
刊名	CURRENT ALZHEIMER RESEARCH
	2019
卷号	16 期号:8 页码:710-722
关键词	Resveratrol Alzheimer's disease tau oligomer neuroinflammation synapse loss
ISSN号	1567-2050
DOI	10.2174/1567205016666190801153751
英文摘要	Alzheimer's Disease (AD) is characterized by the presence of extracellular amyloid-beta (A beta) plaques and intraneuronal neurofibrillary tangles assembled by the microtubule-associated protein tau. Increasing evidence demonstrated that tau pathology played an important role in AD progression. Resveratrol (RSV) has previously proved to exert neuroprotective effect against AD by inhibiting A beta generation and A beta-induced neurocytotoxicity, while its effect on tau pathology is still unknown. Methods: The effect of RSV on tau aggregation was measured by Thioflavin T fluorescence and Transmission electron microscope imaging. The effect of RSV on tau oligomer-induced cytotoxicity was assessed by MTT assay and the uptake of extracellular tau by N2a cells was determined by immunocytochemistry. 6-month-old male PS19 mice were treated with RSV or vehicle by oral administration (gayage) once a day for 5 weeks. The cognitive performance was determined using Morris water maze test, object recognition test and Y-maze test. The levels of phosphorylated-tau, gliosis, proinflammatory cytokines such as TNF-alpha and IL-beta, and synaptic proteins including synaptophysin and PSD95 in the brains of the mice were evaluated by immunoblotting, immunostaining and ELISA, respectively. Results: RSV significantly inhibited tau aggregation and tau oligomer-induced cytotoxicity, and blocked the uptake of extracellular tau oligomers by N2a cells. When applied to PS19 mice, RSV treatment effectively rescued cognitive deficits, reducing the levels of phosphorylated tau, neuroinflammation and synapse loss in the brains of mice. Conclusion: These findings suggest that RSV has promising therapeutic potential for AD and other tauopathies.
资助项目	National Science and Technology Major Projects of New Drugs[2018ZX09301032] ; National Science and Technology Major Projects of New Drugs[2018ZX09733001-001-008] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040215]
WOS关键词	PAIRED HELICAL FILAMENTS ; ALZHEIMERS-DISEASE ; PROTEIN-TAU ; NEURODEGENERATION ; NEUROINFLAMMATION ; PATHOPHYSIOLOGY ; PHOSPHORYLATION ; OLIGOMERS ; TANGLES ; BETA
WOS研究方向	Neurosciences & Neurology
语种	英语
出版者	BENTHAM SCIENCE PUBL LTD
WOS记录号	WOS:000489741300003
资助机构	National Science and Technology Major Projects of New Drugs ; Strategic Priority Research Program of the Chinese Academy of Sciences
内容类型	期刊论文
源URL	[http://ir.ipe.ac.cn/handle/122111/31269]
专题	中国科学院过程工程研究所
通讯作者	Yu, Xiao-Lin; Liu, Rui-Tian
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Univ Auckland, Auckland 1023, New Zealand 3.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
推荐引用方式 GB/T 7714	Sun, Xiao-Ying,Dong, Quan-Xiu,Zhu, Jie,et al. Resveratrol Rescues Tau-Induced Cognitive Deficits and Neuropathology in a Mouse Model of Tauopathy[J]. CURRENT ALZHEIMER RESEARCH,2019,16(8):710-722.
APA	Sun, Xiao-Ying.,Dong, Quan-Xiu.,Zhu, Jie.,Sun, Xun.,Zhang, Li-Fan.,...&Liu, Rui-Tian.(2019).Resveratrol Rescues Tau-Induced Cognitive Deficits and Neuropathology in a Mouse Model of Tauopathy.CURRENT ALZHEIMER RESEARCH,16(8),710-722.
MLA	Sun, Xiao-Ying,et al."Resveratrol Rescues Tau-Induced Cognitive Deficits and Neuropathology in a Mouse Model of Tauopathy".CURRENT ALZHEIMER RESEARCH 16.8(2019):710-722.