Tetrahydroxy stilbene glucoside improved the behavioral disorders of APP695V717I transgenic mice by inhibiting the expression of Beclin-1 and LC3-II.
Tetrahydroxy stilbene glucoside improved the behavioral disorders of APP695V717I transgenic mice by inhibiting the expression of Beclin-1 and LC3-II.
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DOI：
10.1016/s0254-6272(15)30100-x
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Hongbo R. Luo;Yun Li;Jian-kui Guo;Zunjin Liu;Zhi-qiang Zhang;Yong Wang;Zhao Liu;Xiangqun Shi
中科院分区：
文献类型：
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作者：
Hongbo R. Luo;Yun Li;Jian-kui Guo;Zunjin Liu;Zhi-qiang Zhang;Yong Wang;Zhao Liu;Xiangqun Shi
目的观察四羟基二苯乙烯苷（tetrahydroxystilbene glucoside，TSG）对APP 695 V717 I转基因小鼠行为学及自噬相关蛋白Beclin-1和LC 3-II表达的影响。正常对照组由相同年龄和背景的C57 BL/6 J小鼠组成（n= 20）。TSG组给予TSG灌胃1个月。使用Morris水迷宫和Y-迷宫测试测量行为。结果模型组小鼠逃避电刺激次数明显增加，Morris水迷宫实验显示逃避潜伏期延长，游泳距离增加，穿越前平台位置所需时间缩短，Beclin-1和LC 3-II的mRNA和蛋白表达均高于对照组（P< 0.05）。TSG组的电刺激逃避次数减少，逃避潜伏期和游泳距离缩短，穿越前平台位置所需的时间延长，Beclin-1和LC 3-II的mRNA和蛋白表达较模型组降低结论二苯乙烯苷可降低自噬通路中Beclin-1和LC 3-II的表达。它能减轻Ab神经毒性引起的内质网功能损伤，改善小鼠的学习、记忆和空间定向行为。
ObjectiveTo observe the effect of tetrahydroxy stilbene glucoside (TSG) on the behavior of APP695V717I transgenic mouse models and the expression of autophagy-associated proteins Beclin-1 and LC3-II.MethodsForty 3-month-old APP695V717I transgenic mice were randomized equally into either a TSG group (n= 20) or a model group (n= 20). A normal control group consisted of C57BL/6J mice of the same age and background (n= 20). The TSG group received TSG intragastric administration for 1 month. Behavior was measured using the Morris water maze and the Y-maze tests. Changes in protein expression and mRNA of autophagy-associated Beclin-1 and LC3-II in mice hippocampus were detected by western blot and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) analyses.ResultsThe number of electric-stimulus escapes significantly increased and the Morris water maze test showed prolonged escape latency, greater swimming distance, less time taken to cross the exact former platform location in the model group, and increased mRNA and protein expressions of Beclin-1 and LC3-II compared with the control group (P< 0.05). The TSG group showed a decrease in the number of electric-stimulus escapes, shorter escape latency and swimming distance, greater time taken to cross the exact former platform location, and decreased mRNA and protein expressions of Beclin-1 and LC3-II compared with the model group (P< 0.05).ConclusionThese results indicate that tetrahydroxy stilbene glucoside can decrease expressions of Beclin-1 and LC3-II in the autophagy pathway. It can attenuate injury to endoplasmic reticulum functions caused by Ab neurotoxicity, improving learning, memorizing, and spatial orientation behavior in mice.