Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室 > 学习记忆的分子神经机制

	Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats
	Ren QG[]1; Wang YJ 1; Gong WG 1; Xu L 2,3; Zhang ZJ[]1
刊名	Journal of Alzheimer’s Disease
	2015
卷号	47 期号:1 页码:61-71
关键词	Alzheimer's disease escitalopram PKA tau
通讯作者	renqingguo1976@163.com ; zhijunzhang@seu.edu.cn
英文摘要	Here, we investigated the effect of escitalopram pretreatment on protein kinase A (PKA)-induced tau hyperphosphorylation and spatial memorydeficits in rats using western blot and behavioral tests, respectively. We demonstrated that escitalopram effectively ameliorated tauhyperphosphorylation and the spatial memory deficits induced by PKA activation. We measured the total and activity-dependent Ser9-phosphorylated levels of glycogen synthase kinase (GSK)-3β in hippocampal extracts. No significant change in the total level of GSK-3β was observed between the different groups. However, compared with forskolin injection alone, pretreatment with escitalopram increased the level of Ser9-phosphorylated GSK-3β. We also demonstrated that escitalopram increased Akt phosphorylation at Ser473 (the active form of Akt). Furthermore, we identified other important kinases and phosphatases, such as protein phosphatase 2A, extracellular signal-regulated kinases 1 and 2, and MAP kinase kinase-1/2, that have previously been reported to play a crucial role in tau phosphorylation; however, we did not detect any significant change in the activation of these kinases or phosphatases in our study. We unexpectedly demonstrated that forskolin caused anxiety-like behavior in rats, and pretreatment withescitalopram did not significantly ameliorate the anxiety-like behavior induced by forskolin. These data provide the first evidence that escitalopramameliorates forskolin-induced tau hyperphosphorylation and spatial memory impairment in rats; these effects do not occur via the anti-anxiety activity of escitalopram but may involve the Akt/GSK-3β signaling pathway.
资助信息	This work was supported in part by grants from the National Natural Science Foundation of China (91232707),GrantsfromNationalBasicResearchPro- gram of China (2013CB835103), Strategic Priority Research Program of Chinese Academy of Science (XDB02020002), The Fundamental Research Funds fortheCentralUniversities,andtheordinaryuniversity graduate research and innovation program in Jiangsu Province (KYLX 0200).
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/9434]
专题	昆明动物研究所_学习记忆的分子神经机制昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位	1.Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China 2.Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China 3.Graduate School of Chinese Academy of Sciences, Beijing, China
推荐引用方式 GB/T 7714	Ren QG[*],Wang YJ,Gong WG,et al. Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats[J]. Journal of Alzheimer’s Disease,2015,47(1):61-71.
APA	Ren QG[],Wang YJ,Gong WG,Xu L,&Zhang ZJ[].(2015).Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats.Journal of Alzheimer’s Disease,47(1),61-71.
MLA	Ren QG[*],et al."Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats".Journal of Alzheimer’s Disease 47.1(2015):61-71.