title: Identification of Novel Key Molecules Involved in Spatial Memory Impairment in Triple Transgenic Mice of Alzheimer's Disease.
abstract: The molecular mechanisms underlying cognitive impairment in Alzheimer's disease (AD) remain largely unclear. In the present study, we were aimed to identify the potential key molecules involved in spatial memory impairment in a triple transgenic (3xTg-AD) mouse model of AD. By employing two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry, we revealed a total of 24 differentially expressed proteins in hippocampus of 9-month-old 3xTg-AD mice with significant spatial memory impairment in comparison to the age-matched controls. These differentially expressed proteins can be categorized into several functional classifications that are related to synaptic/memory-, energy metabolism-, intracellular transport-, cell cycle-, cellular defense and structure, and stress response. To further verify the target proteins that may underlie the memory deficits, we pre-treated the 3xTg-AD mice for 3 months with coenzyme Q10 (CoQ10) (800 mg/kg body weight/day), a powerful endogenous antioxidant that has been shown to be able to prevent memory deficits in several AD mouse models. We found that administration of CoQ10 altered the expression levels of nine proteins in hippocampus of 3xTg-AD mice with simultaneous improvement of spatial memory. Interestingly, complexin-1/2, two molecules which were shown to alter LTP, were modulated (i.e., the levels were reduced in 3xTg-AD mice and CoQ10 restored the levels) in response to CoQ10 treatment among these nine proteins. Furthermore, we found that adeno-associated virus serotype 9 (AAV-9)-mediated overexpression of complexin-1/2 prevented memory impairment in the AD mouse model. Taken together, this study has identified a number of differentially expressed proteins in hippocampus of 3xTg-AD mice and the control in presence or absence of CoQ10. The modulation of complexin-1/2 expression by CoQ10 may contribute to the amelioration of memory impairment in the AD transgenic mice.
authors.affiliation: Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ying
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, No. 8, Longyuan Road, Nanshan District, Shenzhen, 518055, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Sui
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, No. 8, Longyuan Road, Nanshan District, Shenzhen, 518055, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, No. 8, Longyuan Road, Nanshan District, Shenzhen, 518055, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Neurology, Shanghai Jiaotong University Affiliated the Sixth Hospital, Shanghai, 200233, China.
authors.forename: Zhongsen
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Shen Zhen Kai-Tuo Biotech, Shenzhen, 518010, China.|Guang Zhou Kai-Tuo Biotech, Guangzhou, 510800, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Luo
authors.affiliation: Laboratory of Neurodegenerative Diseases, Department of Anatomy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Raymond Chuen-Chung
authors.initials: RC
authors.lastname: Chang
authors.affiliation: Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Jiazuan
authors.initials: J
authors.lastname: Ni
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, No. 8, Longyuan Road, Nanshan District, Shenzhen, 518055, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, No. 8, Longyuan Road, Nanshan District, Shenzhen, 518055, China. xifeiyang@gmail.com.
authors.forename: Xifei
authors.initials: X
authors.lastname: Yang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D015153:Blotting, Western; D000229:Dependovirus / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D063990:Gene Ontology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008569:Memory Disorders / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D008822:Mice, Transgenic; D060066:Protein Interaction Maps; D040901:Proteomics; D015203:Reproducibility of Results; D065852:Spatial Memory; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D014451:Ubiquinone; C024989:coenzyme Q10
keywords: Adeno-associated virus; Alzheimer’s disease; Memory; Proteomic analysis; Triple (PS1M146V/APPSwe/TauP301L) transgenic mice