摘要
阿尔茨海默氏病(AD)是老年痴呆的最常见原因,影响全世界超过3600万人。人们发现:八齿鼠,一种南美洲啮齿动物,自发显露AD的神经病理学标志,包括β-淀粉样蛋白(Aβ)和微管相关蛋白沉积以及认知能力随年龄下降。首先,目前的研究引入了一个新颖的对八齿鼠的行为评估法——挖掘实验,这似乎是检测阿尔茨海默氏病八齿鼠模型的神经退行性病变的一种有效手段。因为典型物种行为中的许多这类变化与日常生活活动能力(ADL)受损及人类阿尔茨海默氏病特征的关联性, 这种表征可能产生广泛的影响。其次,现代研究从基因学的角度证明八齿鼠具有类似阿尔茨海默氏病的神经病理学特性,并揭示许多以前未报告的AD生物学标志物:淀粉样前体蛋白(APP)、载脂蛋白E(ApoE)、NFE2L2和PPAR通路的氧化应力基因以及促炎细胞因子和补体蛋白,这些符合已知的神经退行性病变与神经炎症反应之间的联系。总之,目前的结果从行为、细胞和分子水平证实八齿鼠具有与阿尔茨海默氏病相同的自发性神经病理学特性。这些特点使八齿鼠成为在AD发病机理和治疗方法研究中的一种独特的自然啮齿动物模型。
关键词: 阿尔茨海默氏病;β-淀粉样蛋白;挖掘实验;补体;细胞因子;八齿鼠
Current Alzheimer Research
Title:Natural AD-Like Neuropathology in Octodon degus: Impaired Burrowing and Neuroinflammation
Volume: 12 Issue: 4
Author(s): Robert M.J. Deacon, Francisco J. Altimiras, Enrique A. Bazan-Leon, Rhada D. Pyarasani, Fabiane M. Nachtigall, Leonardo S. Santos, Anthony G. Tsolaki, Lina Pednekar and Uday Kishore, Rodolfo R. Biekofsky, Rodrigo A. Vasquez and Patricia Cogram
Affiliation:
关键词: 阿尔茨海默氏病;β-淀粉样蛋白;挖掘实验;补体;细胞因子;八齿鼠
摘要: Alzheimer’s disease (AD) is the most common cause of dementia, affecting more than 36 million people worldwide. Octodon degus, a South American rodent, has been found to spontaneously develop neuropathological signs of AD, including amyloid-β (Aβ) and tau deposits, as well as a decline in cognition with age. Firstly, the present work introduces a novel behavioral assessment for O. degus - the burrowing test - which appears to be a useful tool for detecting neurodegeneration in the O. degus model for AD. Such characterization has potentially wide-ranging implications, because many of these changes in species-typical behaviors are reminiscent of the impairments in activities of daily living (ADL), so characteristic of human AD. Furthermore, the present work characterizes the ADlike neuropathology in O. degus from a gene expression point of view, revealing a number of previously unreported AD biomarkers, which are found in human AD: amyloid precursor protein (APP), apolipoprotein E (ApoE), oxidative stressrelated genes from the NFE2L2 and PPAR pathway, as well as pro-inflammatory cytokines and complement proteins, in agreement with the known link between neurodegeneration and neuroinflammation. In summary, the present results confirm a natural neuropathology in O. degus with similar characteristics to AD at behavioral, cellular and molecular levels. These characteristics put O. degus in a singular position as a natural rodent model for research into AD pathogenesis and therapeutics against AD.
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Robert M.J. Deacon, Francisco J. Altimiras, Enrique A. Bazan-Leon, Rhada D. Pyarasani , Fabiane M. Nachtigall, Leonardo S. Santos, Anthony G. Tsolaki, Lina Pednekar and Uday Kishore, Rodolfo R. Biekofsky, Rodrigo A. Vasquez and Patricia Cogram , Natural AD-Like Neuropathology in Octodon degus: Impaired Burrowing and Neuroinflammation, Current Alzheimer Research 2015; 12 (4) . https://dx.doi.org/10.2174/1567205012666150324181652
DOI https://dx.doi.org/10.2174/1567205012666150324181652 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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