首页> 外文期刊>Metabolic brain disease >Donepezil improves the cognitive impairment in a tree shrew model of Alzheimer's disease induced by amyloid-beta(1-40) via activating the BDNF/TrkB signal pathway
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Donepezil improves the cognitive impairment in a tree shrew model of Alzheimer's disease induced by amyloid-beta(1-40) via activating the BDNF/TrkB signal pathway

机译:Doypezil通过激活BDNF / TRKB信号途径来提高由淀粉样蛋白-β(1-40)诱导的阿尔茨海默病的树木血腥模型中的认知障碍

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摘要

Alzheimer's disease (AD) is a chronic neurodegenerative disorder which can contribute to memory loss and cognitive damage in the elderly; moreover, evidence from clinical and animal studies demonstrated that AD always exhibit severe cognitive deficits. However, the effects of donepezil medications on cognition are controversial. Additionally, it is unclear whether donepezil can protect neurons to improve cognitive function through the brain-derived neurotropic factor (BDNF)/tyrosine receptor kinase B (TrkB) signalling pathway in the tree shrew (TS), which has a closer evolutionary relationship to primates than rodents. Here, we designed a study on an amyloid-beta(1-40) (A beta(1-40))-induced TS model of AD and investigated the molecular mechanism by which donepezil protects neurons and improves cognitive function through activating the BDNF/TrkB signalling pathway. The results showed that donepezil could rescue A beta(1-40)-induced spatial cognition deficits, and reverse A beta(1-40)-induced temporal horn along with ADC enlargement in the TS brain. Meanwhile, it suppressed A beta(1-40)-induced neuronal damage and loss of body weight. Intriguingly, donepezil could increase the choline acetyl transferase (ChAT) expression level and reduce the fibrillary acid protein (GFAP) expression level in the hippocampus and cortex of TS. Additionally, donepezil significantly upregulated the expression level of BDNF, as well as the phosphorylated level of TrkB. These results suggested that donepezil could protect neurocytes from senility and ameliorate learning and memory impairment in the TS model of AD, which appeared to be through regulating the cholinergic system and inhibiting the BDNF/TrkB-dependent signalling pathway. Moreover, the study underlines the potency of TS to be a novel animal model for research on AD, and it deserves intensive attention.
机译:阿尔茨海默病(AD)是一种慢性神经变性障碍,可以有助于老年人的记忆丧失和认知损害;此外,来自临床和动物研究的证据表明,广告始终表现出严重的认知缺陷。然而,Deypezil药物对认知的影响是有争议的。另外,目前尚不清楚Dentpezil是否可以保护神经元通过树血液(TS)中的脑衍生的神经熵因子(BDNF)/酪氨酸受体激酶B(TRKB)信号传导途径来保护神经元以改善认知功能,这具有与灵长类动物更近的进化关系比啮齿动物。在这里,我们设计了对淀粉样蛋白-β(1-40)的研究(β(1-40)) - 诱导的AD TS模型,并研究了多奈哌齐保护神经元并通过激活BDNF /改善认知功能的分子机制TRKB信号通路。结果表明,Dempezil可以拯救β(1-40)诱导的空间认知缺陷,并反转β(1-40)诱导的时间喇叭以及TS脑中的ADC扩大。同时,它抑制了β(1-40) - 诱导的神经元损伤和体重丧失。有趣的是,Deppezil可以增加胆碱乙酰转移酶(聊天)表达水平,并减少海马中的纤维酸蛋白(GFAP)表达水平和Ts的皮质。此外,DepPezil显着上调了BDNF的表达水平,以及Trkb的磷酸化水平。这些结果表明,Depepezil可以保护神经细胞免受衰老和AD的TS模型中的改善学习和记忆障碍,这似乎是通过调节胆碱能系统并抑制BDNF / TRKB依赖的信号通路。此外,该研究强调了TS的效力是对广告研究的新型动物模型,值得注意的关注。

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