PMID- 27335030
OWN - NLM
STAT- MEDLINE
DCOM- 20180309
LR  - 20181113
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 54
IP  - 5
DP  - 2017 Jul
TI  - Identification of Novel Key Molecules Involved in Spatial Memory Impairment in 
      Triple Transgenic Mice of Alzheimer's Disease.
PG  - 3843-3858
LID - 10.1007/s12035-016-9959-2 [doi]
AB  - 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.
FAU - Ying, Ming
AU  - Ying M
AD  - 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.
FAU - Sui, Xiaojing
AU  - Sui X
AD  - Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease 
      Control and Prevention, No. 8, Longyuan Road, Nanshan District, Shenzhen, 518055, 
      China.
FAU - Zhang, Yanling
AU  - Zhang Y
AD  - Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease 
      Control and Prevention, No. 8, Longyuan Road, Nanshan District, Shenzhen, 518055, 
      China.
FAU - Sun, Qian
AU  - Sun Q
AD  - Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease 
      Control and Prevention, No. 8, Longyuan Road, Nanshan District, Shenzhen, 518055, 
      China.
FAU - Qu, Zhongsen
AU  - Qu Z
AD  - Department of Neurology, Shanghai Jiaotong University Affiliated the Sixth 
      Hospital, Shanghai, 200233, China.
FAU - Luo, Xiaobin
AU  - Luo X
AD  - Shen Zhen Kai-Tuo Biotech, Shenzhen, 518010, China.
AD  - Guang Zhou Kai-Tuo Biotech, Guangzhou, 510800, China.
FAU - Chang, Raymond Chuen-Chung
AU  - Chang RC
AD  - Laboratory of Neurodegenerative Diseases, Department of Anatomy, LKS Faculty of 
      Medicine, The University of Hong Kong, Hong Kong, China.
FAU - Ni, Jiazuan
AU  - Ni J
AD  - 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.
FAU - Liu, Jianjun
AU  - Liu J
AD  - Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease 
      Control and Prevention, No. 8, Longyuan Road, Nanshan District, Shenzhen, 518055, 
      China.
FAU - Yang, Xifei
AU  - Yang X
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160622
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 1339-63-5 (Ubiquinone)
RN  - EJ27X76M46 (coenzyme Q10)
SB  - IM
MH  - Alzheimer Disease/drug therapy/*pathology/*physiopathology
MH  - Animals
MH  - Blotting, Western
MH  - Dependovirus/metabolism
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Gene Ontology
MH  - Hippocampus/drug effects/metabolism
MH  - Humans
MH  - Memory Disorders/drug therapy/*pathology/*physiopathology
MH  - Mice, Transgenic
MH  - Protein Interaction Maps
MH  - Proteomics
MH  - Reproducibility of Results
MH  - *Spatial Memory
MH  - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
MH  - Tandem Mass Spectrometry
MH  - Ubiquinone/analogs & derivatives/pharmacology/therapeutic use
OTO - NOTNLM
OT  - Adeno-associated virus
OT  - Alzheimer's disease
OT  - Memory
OT  - Proteomic analysis
OT  - Triple (PS1M146V/APPSwe/TauP301L) transgenic mice
EDAT- 2016/06/24 06:00
MHDA- 2018/03/10 06:00
CRDT- 2016/06/24 06:00
PHST- 2015/11/08 00:00 [received]
PHST- 2016/06/06 00:00 [accepted]
PHST- 2016/06/24 06:00 [pubmed]
PHST- 2018/03/10 06:00 [medline]
PHST- 2016/06/24 06:00 [entrez]
AID - 10.1007/s12035-016-9959-2 [pii]
AID - 10.1007/s12035-016-9959-2 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2017 Jul;54(5):3843-3858. doi: 10.1007/s12035-016-9959-2. Epub 
      2016 Jun 22.