Shi Jing, Zhang Xuekai, Ni Jingnian, Wei Mingqing, Li Ting, Zhou Bingling, Liu Xiawei, Zhang Liping, Wang Pengwen, Tian Jinzhou, Wang Yongyan
Third Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Department of Radiology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Alzheimers Dement (N Y). 2018 Dec 14;4:724-736. doi: 10.1016/j.trci.2018.10.008. eCollection 2018.
The degeneration of memory-focused synapses play important roles in Alzheimer's disease (AD) pathogenesis, while it is not well known how β amyloid interferes neuron apoptosis and how a herbal combination GAPT influence synapse loss and neuronal apoptosis pathways of APP/PS1 transgenic mice.
Three-month and six-month APPswe/PS1dE9 transgenic mice were used. Spatial and memory ability were measured by Morris Water Maze, Neuron and synapse number were assessed by electron microscope; Aβ, Bcl-2/Bax were determined by immunohistochemistry and western blot.
APP/PS1 mice not only had increased Aβ accumulation, impaired memory performance, less synapse number, and much more necrosed neurons, but also had significant reduction in the Bcl-2/Bax ratio. However, GAPT and donepezil showed improved memory performance, less Aβ accumulation, increased neuron and synapse number, as well as restored balance of Bcl-2/Bax.
GAPT may improve cognitive functions via both reducing Aβ deposition and restoring Bcl-2/Bax balance of neuron.
聚焦记忆的突触退化在阿尔茨海默病（AD）发病机制中起重要作用，然而，β淀粉样蛋白如何干扰神经元凋亡以及草药组合GAPT如何影响APP/PS1转基因小鼠的突触丢失和神经元凋亡途径尚不清楚。
使用3个月和6个月大的APPswe/PS1dE9转基因小鼠。通过莫里斯水迷宫测量空间和记忆能力，通过电子显微镜评估神经元和突触数量；通过免疫组织化学和蛋白质印迹法测定Aβ、Bcl-2/Bax。
APP/PS1小鼠不仅Aβ积累增加、记忆表现受损、突触数量减少且坏死神经元更多，而且Bcl-2/Bax比值显著降低。然而，GAPT和多奈哌齐显示出记忆表现改善、Aβ积累减少、神经元和突触数量增加以及Bcl-2/Bax平衡恢复。
GAPT可能通过减少Aβ沉积和恢复神经元的Bcl-2/Bax平衡来改善认知功能。
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