T-006 Improves Learning and Memory Function and Regulates Synaptic Associated Protein Expression in APP/PS1/Tau Triple Transgenic Mice
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0504
- VernacularTitle:T-006改善APP/PS1/Tau转基因小鼠学习记忆功能及调控突触相关蛋白表达
- Author:
Jie-hong CHENG
1
;
Gui-liang ZHANG
2
;
Bao-jian GUO
2
;
Ye-wei SUN
2
;
Gao-xiao ZHANG
2
;
Yu-qiang WANG
2
;
Zai-jun ZHANG
2
Author Information
1. The First Affiliated Hospital， Guangzhou University of Chinese Medicine， Guangzhou 510405， China
2. Institute of New Drug Research， College of Pharmacy， Jinan University， Guangzhou 510632， China
- Publication Type:Journal Article
- Keywords:
tetramethylpyrazine derivative T-006;
APP/PS1/Tau;
Alzheimer’s disease;
synaptic proteins;
learning and memory
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2021;42(5):667-675
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the efficacy and mechanism of tetramethylpyrazine derivative T-006 on learning and memory function of APP/PS1/Tau transgenic （3×Tg） mice. MethodsEight-month-old 3×Tg mice and their wild-type （WT） littermates were divided into WT group， WT+T-006 （10 mg/kg） group， 3×Tg group， low-dose T-006 group （1 mg/kg）， medium-dose T-006 group （3 mg/kg）， high-dose T-006 group （10 mg/kg）， donepezil group （1.3 mg/kg） and memantine group （5 mg/kg）. Within 4 months， T-006 and donepezil were continuously administered once a day and memantine twice a day. Behavioral tests including novel object recognition， step-down avoidance and morris water maze were performed to evaluate learning and memory function of mice. Immunohistochemistry was used to observe the deposition of amyloid plaques in the hippocampus of mice. Western blotting was employed to detect the protein expression of APP， BACE-1， PSD95， synapsin I， synapsin Ⅱ， synaptophysin， BDNF， CREB and p-CREB. ResultsT-006 treatment reduced the numbers of errors in the step-down avoidance test （P< 0.05）， significantly reduced the APP expression and increased the expression of PSD95， synaptophysin， synapsin I and BDNF （P<0.05）. ConclusionT-006 improves the learning and memory function of 3×Tg mice and reduces the APP expression， which may be explained by the increase of synaptic associated protein expression.
