摘要
阿尔茨海默病症(AD)是老年人痴呆最常见的原因,其特点是认知和记忆的缺陷。虽然β-淀粉样蛋白(Aβ)的积累是已知的最早的病理事件,但是触发随后的神经退行性疾病,β-淀粉样蛋白的积累如何导致的行为赤字仍然不完全理解。在这项研究中,采用Morris水迷宫试验、ELISA和体视学方法,我们研究了空间学习和记忆能力,可溶性β-淀粉样蛋白浓度和髓鞘的纤维在4 -,6 -,8 -海马和10个月大的Tg2576转基因阿尔茨海默病症模型小鼠。我们的研究结果表明,较野生型(WT)控制小鼠,Tg2576小鼠空间学习记忆能力明显受损,10个月年龄时,有髓神经纤维长度在海马齿状回(DG)明显减少,从野生型控制小鼠0.33±0.03公里到在Tg2576小鼠0.17±0.02公里。然而,水溶性β-淀粉样蛋白40和β-淀粉样蛋白42浓度早在4-6月龄显著增加。下降的有髓神经纤维长度在海马齿状回可能导致Tg2576小鼠空间学习记忆障碍。因此,我们认为,水溶性β-淀粉样蛋白显著积累可作为阿尔茨海默病症的诊断的临床生物标志物,以及保护的有髓神经纤维可能代表了一种新的延缓早期阿尔茨海默病症的发展
关键词: 阿尔茨海默病,β-淀粉样蛋白,海马,有髓纤维,体视学,Tg2576小鼠
Current Alzheimer Research
Title:Decreased Myelinated Fibers in the Hippocampal Dentate Gyrus of the Tg2576 Mouse Model of Alzheimer’s Disease
Volume: 13 Issue: 9
Author(s): Wei Lu, Shu Yang, Lei Zhang, Lin Chen, Feng-Lei Chao, Yan-min Luo, Qian Xiao, Heng-Wei Gu, Rong Jiang, Yong Tang
Affiliation:
关键词: 阿尔茨海默病,β-淀粉样蛋白,海马,有髓纤维,体视学,Tg2576小鼠
摘要: Alzheimer’s disease (AD), the most common cause of dementia in the elderly, is characterized by deficits in cognition and memory. Although amyloid-β (Aβ) accumulation is known to be the earliest pathological event that triggers subsequent neurodegeneration, how Aβ accumulation causes behavioral deficits remains incompletely understood. In this study, using the Morris water maze test, ELISA and stereological methods, we examined spatial learning and memory performance, the soluble Aβ concentration and the myelination of fibers in the hippocampus of 4-, 6-, 8- and 10-month-old Tg2576 AD model mice. Our results showed that spatial learning and memory performance was significantly impaired in the Tg2576 mice compared to the wild type (WT) controls and that the myelinated fiber length in the hippocampal dentate gyrus (DG) was markedly decreased from 0.33 ± 0.03 km in the WT controls to 0.17 ± 0.02 km in the Tg2576 mice at 10 months of age. However, the concentrations of soluble Aβ40 and Aβ42 were significantly increased as early as 4-6 months of age. The decreased myelinated fiber length in the DG may contribute to the spatial learning and memory deficits of Tg2576 mice. Therefore, we suggest that the significant accumulation of soluble Aβ may serve as a preclinical biomarker for AD diagnosis and that protecting myelinated fibers may represent a novel strategy for delaying the progression of early-stage AD.
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Cite this article as:
Wei Lu, Shu Yang, Lei Zhang, Lin Chen, Feng-Lei Chao, Yan-min Luo, Qian Xiao, Heng-Wei Gu, Rong Jiang, Yong Tang , Decreased Myelinated Fibers in the Hippocampal Dentate Gyrus of the Tg2576 Mouse Model of Alzheimer’s Disease, Current Alzheimer Research 2016; 13 (9) . https://dx.doi.org/10.2174/1567205013666160314150709
DOI https://dx.doi.org/10.2174/1567205013666160314150709 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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