Ginsenoside Rg1 ameliorates hippocampal long-term potentiation and memory in an Alzheimer's disease model
Ginsenoside Rg1 ameliorates hippocampal long-term potentiation and memory in an Alzheimer's disease model
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DOI：
10.3892/mmr.2016.5103
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发表时间：
2016-06-01
影响因子：
3.4
通讯作者：
Niu, Qingliang
中科院分区：
文献类型：
--
作者：
Li, Fengling;Wu, Xiqing;Niu, Qingliang
阿尔茨海默病（AD）复杂的发病机制限制了有效治疗药物的研究进展。淀粉样蛋白前体蛋白（APP）和早老素-1 （PS1）在AD中总是过表达，被认为是-淀粉样斑块形成和AD症状的启动因子。本研究通过过表达APP和PS1构建转基因AD模型，验证人参皂苷Rg1对记忆性能和突触可塑性的保护作用。6月龄AD小鼠腹腔注射0.1 ~ 10 mg/kg人参皂苷Rg1。治疗后测量长期记忆、突触可塑性以及ad相关蛋白和突触可塑性相关蛋白的水平。用恐惧条件反射任务测量记忆，用免疫印迹法研究蛋白质表达水平。所有数据均采用单因素方差分析或t检验进行分析。连续给药30 d后，10 mg/kg人参皂苷Rg1给药组可改善AD小鼠模型的记忆。生化实验表明，人参皂苷Rg1处理可减少AD模型中-淀粉样蛋白1-42的积累，并磷酸化(p)-Tau。此外，脑源性神经营养因子（BDNF）和p-TrkB突触可塑性相关蛋白在人参皂苷Rg1应用后上调。相应的，人参皂苷Rg1在AD小鼠模型中恢复了长期增强（LTP）。总之，人参皂苷Rg1修复了海马LTP和记忆，可能是通过促进ad相关蛋白的清除和激活BDNF-TrkB途径。因此，人参皂苷Rg1可能是治疗AD的候选药物。
The complex etiopathogenesis of Alzheimer's disease (AD) has limited progression in the identification of effective therapeutic agents. Amyloid precursor protein (APP) and presenilin-1 (PS1) are always overexpressed in AD, and are considered to be the initiators of the formation of -amyloid plaques and the symptoms of AD. In the present study, a transgenic AD model, constructed via the overexpression of APP and PS1, was used to verify the protective effects of ginsenoside Rg1 on memory performance and synaptic plasticity. AD mice (6-month-old) were treated via intraperitoneal injection of 0.1-10 mg/kg ginsenoside Rg1. Long-term memory, synaptic plasticity, and the levels of AD-associated and synaptic plasticity-associated proteins were measured following treatment. Memory was measured using a fear conditioning task and protein expression levels were investigated using western blotting. All the data was analyzed by one-way analysis of variance or t-test. Following 30 days of consecutive treatment, memory in the AD mouse model was ameliorated in the 10 mg/kg ginsenoside Rg1 treatment group. As demonstrated by biochemical experiments, ginsenoside Rg1 treatment reduced the accumulations of -amyloid 1-42 and phosphorylated (p)-Tau in the AD model. Additionally, brain-derived neurotrophic factor (BDNF) and p-TrkB synaptic plasticity-associated proteins were upregulated following ginsenoside Rg1 application. Correspondingly, long-term potentiation (LTP) was restored following ginsenoside Rg1 application in the AD mice model. Taken together, ginsenoside Rg1 repaired hippocampal LTP and memory, likely through facilitating the clearance of AD-associated proteins and through activation of the BDNF-TrkB pathway. Therefore, ginsenoside Rg1 may be a candidate drug for the treatment of AD.