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多萜醇减轻 APP/PS1 小鼠的认知功能障碍和神经病理学改变。

Polyprenols mitigate cognitive dysfunction and neuropathology in the APP/PS1 mouse.

机构信息

Department of Pharmacology, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.

Institute of Chemical Industry of Forest Products, CAF, National Engineering Lab for Biomass Chemical Utilization, Key and Open Lab of Forest Chemical Engineering, SFA, Key Lab of Biomass Energy and Material, Nanjing, Jiangsu, 210042, China.

出版信息

Phytother Res. 2018 Jun;32(6):1098-1107. doi: 10.1002/ptr.6050. Epub 2018 Feb 22.

Abstract

Alzheimer's disease (AD) is a very common neurodegenerative disorder in the elderly and brings considerable financial and social problems worldwide. In this study, polyprenols were firstly evaluated the effects on the cognitive deficits and neuropathology in APP/PS1 mice model of AD. At 3 months old, the APP/PS1 mice were divided into model group; polyprenols low, middle, and high dosage group; and positive drug group. Age-matched wild-type mice were chosen in control group. The administration by oral gavage lasted 6 months. Polyprenols treatment significantly improved cognitive impairment of double transgenic mice compared with vehicle control treatment in behavioral tests. In addition, immunohistochemistry and enzyme-linked immunosorbent assay showed that there were significantly reductions in neuritic plaques and the level of hyperphosphorylated tau in brain of polyprenols-treated mice. Furthermore, we found that polyprenols treatment reduced the apoptotic cells in brain sections of 9-month-old APP/PS1 mice. These results reveal that polyprenols exert neuroprotective effects in APP/PS1 mice and could represent an effective treatment for AD.

摘要

阿尔茨海默病(AD)是老年人中非常常见的神经退行性疾病,在全球范围内带来了相当大的经济和社会问题。在这项研究中,首先评估了多萜醇对 AD 模型 APP/PS1 小鼠认知缺陷和神经病理学的影响。在 3 个月大时,将 APP/PS1 小鼠分为模型组;多萜醇低、中、高剂量组;和阳性药物组。选择年龄匹配的野生型小鼠作为对照组。通过口服灌胃给药持续 6 个月。与载体对照组相比,多萜醇治疗显著改善了双转基因小鼠的认知障碍,表现在行为测试中。此外,免疫组织化学和酶联免疫吸附试验显示,多萜醇治疗的小鼠脑中神经原纤维缠结和过度磷酸化 tau 的水平显著降低。此外,我们发现多萜醇治疗可减少 9 个月大 APP/PS1 小鼠脑切片中的凋亡细胞。这些结果表明,多萜醇对 APP/PS1 小鼠具有神经保护作用,可能是 AD 的有效治疗方法。

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