华佗再造丸通过改善突触可塑性和减少 Aβ 沉积改善 APP/PS1 转基因小鼠的认知障碍。
Huatuo Zaizao pill ameliorates cognitive impairment of APP/PS1 transgenic mice by improving synaptic plasticity and reducing Aβ deposition.
机构信息
Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, Jiangsu, People's Republic of China.
Department of Neurology, The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210001, Jiangsu, People's Republic of China.
出版信息
BMC Complement Altern Med. 2018 May 29;18(1):167. doi: 10.1186/s12906-018-2237-2.
BACKGROUND
It is well known that Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory deficits and cognitive decline. Amyloid-β (Aβ) deposition and synaptic dysfunction play important roles in the pathophysiology of Alzheimer's disease (AD). The Huatuo Zaizao pill (HT) is a Traditional Chinese Medicine (TCM) that has been used clinically for many years in China, mainly for post-stroke rehabilitation and cognitive decline; however, the mechanism of cognitive function is not clear. In this study, we investigated the effect of HT on hippocampal synaptic function, Amyloid-β (Aβ) deposition in APP/PS1 AD transgenic mice.
METHOD
Six-month-old APP/PS1 transgenic (Tg) mice were randomly divided into control, HT-treated, and memantine (MEM)-treated groups. Then, these groups were orally administered vehicle (for the control), HT (0.25 g/kg) and MEM (5 mg/kg) respectively for 4 weeks. The Morris water maze, Novel Object Recognition, and Open field tests were used to assess cognitive behavioral changes. We evaluated the effects of HT on neuronal excitability, membrane ion channel activity, and synaptic plasticity in acute hippocampal slices by combining electrophysiological extracellular tests. Synaptic morphology in the hippocampus was investigated by electron microscopy. Western blotting was used to assess synaptic-associated protein and Aβ production and degrading levels. Immunofluorescence staining was used to determine the relative integrated density.
RESULTS
HT can ameliorate hippocampus-dependent memory deficits and improve synaptic dysfunction by reversing LTP impairment in APP/PS1 transgenic mice. Moreover, HT reduces amyloid plaque deposition by regulating α-secretase and γ-secretase levels.
CONCLUSION
HT can improve the learning and memory function of APP/PS1 transgenic mice by improving synaptic function and reducing amyloid plaque deposition.
背景
众所周知，阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是记忆障碍和认知能力下降。β淀粉样蛋白（Aβ）沉积和突触功能障碍在阿尔茨海默病（AD）的病理生理学中起重要作用。华佗再造丸（HT）是一种中药，已在中国临床应用多年，主要用于中风后康复和认知能力下降；然而，其认知功能的机制尚不清楚。在这项研究中，我们研究了 HT 对 APP/PS1 AD 转基因小鼠海马突触功能、β淀粉样蛋白（Aβ）沉积的影响。
方法
将 6 月龄 APP/PS1 转基因（Tg）小鼠随机分为对照组、HT 治疗组和盐酸美金刚（MEM）治疗组。然后，这些组分别口服给予载体（对照组）、HT（0.25g/kg）和 MEM（5mg/kg），持续 4 周。通过 Morris 水迷宫、新物体识别和旷场实验评估认知行为变化。我们通过结合电生理细胞外测试来评估 HT 对急性海马切片中神经元兴奋性、膜离子通道活性和突触可塑性的影响。通过电子显微镜研究海马突触形态。使用 Western blot 检测突触相关蛋白和 Aβ产生和降解水平。免疫荧光染色用于确定相对积分密度。
结果
HT 可改善 APP/PS1 转基因小鼠的海马依赖性记忆障碍，并通过逆转 APP/PS1 转基因小鼠的 LTP 损伤改善突触功能障碍。此外，HT 通过调节α-分泌酶和γ-分泌酶水平减少淀粉样斑块沉积。
结论
HT 通过改善突触功能和减少淀粉样斑块沉积，可提高 APP/PS1 转基因小鼠的学习和记忆功能。
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