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老年中国树鼩的认知缺陷和类似阿尔茨海默病的病理。

Cognitive Deficits and Alzheimer's Disease-Like Pathologies in the Aged Chinese Tree Shrew.

机构信息

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, and KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Kunming, 650204, Yunnan, China.

Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, 650204, Yunnan, China.

出版信息

Mol Neurobiol. 2024 Apr;61(4):1892-1906. doi: 10.1007/s12035-023-03663-7. Epub 2023 Oct 9.

Abstract

Alzheimer's disease (AD) is the most common chronic progressive neurodegenerative disease in the elderly. It has an increasing prevalence and a growing health burden. One of the limitations in studying AD is the lack of animal models that show features of Alzheimer's pathogenesis. The tree shrew has a much closer genetic affinity to primates than to rodents and has great potential to be used for research into aging and AD. In this study, we aimed to investigate whether tree shrews naturally develop cognitive impairment and major AD-like pathologies with increasing age. Pole-board and novel object recognition tests were used to assess the cognitive performance of adult (about 1 year old) and aged (6 years old or older) tree shrews. The main AD-like pathologies were assessed by Western blotting, immunohistochemical staining, immunofluorescence staining, and Nissl staining. Our results showed that the aged tree shrews developed an impaired cognitive performance compared to the adult tree shrews. Moreover, the aged tree shrews exhibited several age-related phenotypes that are associated with AD, including increased levels of amyloid-β (Aβ) accumulation and phosphorylated tau protein, synaptic and neuronal loss, and reactive gliosis in the cortex and the hippocampal tissues. Our study provides further evidence that the tree shrew is a promising model for the study of aging and AD.

摘要

阿尔茨海默病(AD)是老年人中最常见的慢性进行性神经退行性疾病。它的患病率不断增加,给健康带来的负担也越来越重。研究 AD 的一个局限性是缺乏具有阿尔茨海默病发病机制特征的动物模型。树鼩与灵长类动物的遗传亲和力比与啮齿类动物更密切,具有很大的潜力可用于研究衰老和 AD。在这项研究中,我们旨在研究树鼩是否会随着年龄的增长自然发展出认知障碍和主要的 AD 样病理学。杆板和新物体识别测试用于评估成年(约 1 岁)和老年(6 岁或以上)树鼩的认知表现。通过 Western blot、免疫组织化学染色、免疫荧光染色和尼氏染色评估主要的 AD 样病理学。我们的结果表明,与成年树鼩相比,老年树鼩的认知表现受损。此外,老年树鼩表现出几种与 AD 相关的年龄相关表型,包括淀粉样蛋白-β(Aβ)积累和磷酸化 tau 蛋白增加、突触和神经元丧失以及皮质和海马组织中的反应性神经胶质增生。我们的研究进一步证明,树鼩是研究衰老和 AD 的有前途的模型。

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