title: Atorvastatin ameliorates cognitive impairment, Aβ1-42 production and Tau hyperphosphorylation in APP/PS1 transgenic mice.
abstract: Amyloid-beta (Aβ) interacts with the serine/threonine protein kinase AKT (also known as protein kinase B)/glycogen synthase kinase 3β (GSK3β) pathway and deactivates GSK3β signaling, which result in microtubule protein tau phosphorylation. Atorvastatin, a HMG-CoA reductase inhibitor, has been proven to improve learning and memory performance, reduce Aβ and phosphorylated tau levels in mouse model of Alzheimer's disease (AD). However, it still remains unclear whether atorvastatin is responsible for regulation of AKT/GSK3β signaling and contributes to subsequent down-regulation of Aβ1-42 and phosphorylated tau in APP/PS1 transgenic (Tg APP/PS1) mice. Herein, we aimed to investigate the possible impacts of atorvastatin (10 mg/kg, p.o.) on the memory deficit by behavioral tests and changes of AKT/GSK3β signaling in hippocampus and prefrontal cortex by western blot test in Tg APP/PS1 mice. The results showed that treatment with atorvastatin significantly reversed the memory deficit in the Tg APP/PS1 mice in a novel object recognition and the Morris water maze tests. Moreover, atorvastatin significantly attenuated Aβ1-42 accumulation and phosphorylation of tau (Ser396) in the hippocampus and prefrontal cortex of Tg APP/PS1 mice. In addition, atorvastatin treatment also increased phosphorylation of AKT, inhibited GSK3β activity by increasing phosphorylation of GSK3β (Ser9) and decreasing the beta-site APP cleaving enzyme 1 (BACE1) expression. These results indicated that the memory ameliorating effect of atorvastatin may be, in part, by regulation the AKT/GSK3β signaling which may contribute to down-regulation of Aβ1-42 and tau hyperphosphorylation.
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang, 315210, People's of Republic China.|Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's of Republic China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhou
authors.affiliation: School of Nursing, Taishan Medical University, Taian, Shandong, 271016, People's of Republic China.
authors.forename: Huaxia
authors.initials: H
authors.lastname: Liu
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's of Republic China.|Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's of Republic China.
authors.forename: Chenli
authors.initials: C
authors.lastname: Li
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's of Republic China.
authors.forename: Fangyan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang, 315210, People's of Republic China.|Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's of Republic China.
authors.forename: Yaosheng
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang, 315210, People's of Republic China.|Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's of Republic China.
authors.forename: Lingjiang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's of Republic China.|Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's of Republic China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's of Republic China.|Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's of Republic China.
authors.forename: Aiming
authors.initials: A
authors.lastname: Liu
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's of Republic China. zhangjunfang@nbu.edu.cn.|Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's of Republic China. zhangjunfang@nbu.edu.cn.
authors.forename: Junfang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's of Republic China. wangchuang@nbu.edu.cn.|Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's of Republic China. wangchuang@nbu.edu.cn.
authors.forename: Chuang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang, 315210, People's of Republic China. chenzhongming@hotmail.com.|Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's of Republic China. chenzhongming@hotmail.com.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Chen
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D000069059:Atorvastatin
keywords: AKT/GSK3β signaling; Alzheimer’s disease; Atorvastatin; Beta -site APP cleaving enzyme 1; Beta amyloid; Tau