中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (26): 2449-2457.doi: 10.3969/j.issn.1673-5374.2013.26.006

• 原著:退行性病与再生 • 上一篇    下一篇

β淀粉样蛋白能加重脑缺血再灌注后的认知功能损害

  

  • 收稿日期:2013-03-07 修回日期:2013-06-22 出版日期:2013-09-15 发布日期:2013-09-15
  • 基金资助:

    国家高技术研究发展计划（863计划）（2012AA020905），国家自然科学基金（81171143，30971011），国家自然科学基金/香港研究资助局联合研究计划（81161160570），清华大学-裕元医学基金

Amyloid beta-peptide worsens cognitive impairment following cerebral ischemia-reperfusion injury

Bo Song1, 2, Qiang Ao1, 3, Ying Niu2, Qin Shen1, Huancong Zuo3, Xiufang Zhang2, Yandao Gong2   

  1. 1 Research Center of Stem Cells and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China

    2 State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China

    3 Institute of Neurology Disorders, Yuquan Hospital, Tsinghua University, Beijing 100049, China
  • Received:2013-03-07 Revised:2013-06-22 Online:2013-09-15 Published:2013-09-15
  • Contact: Yandao Gong, Master, State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China, gongyd@ tsinghua.edu.cn. Qiang Ao, M.D., Research Center of Stem Cells and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China; Institute of Neurology Disorders, Yuquan Hospital, Tsinghua University, Beijing 100049, China, aoqiang@ tsinghua.edu.cn.
  • About author:Bo Song, M.D.
  • Supported by:

    This work was supported by the National High Technology Research and Development Program of China ("863"Program), No. 2012AA020905; the National Natural Science Foundation of China, No. 81171143 and 30971011; National Natural Science Foundation of China (NSFC)/Research Grants Council (RGC) Joint Research Scheme, No. 81161160570; and Tsinghua- Yue-Yuen Medical Sciences Fund.

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摘要：

阿尔茨海默症患者脑中老年斑的主要成分β淀粉样蛋白及脑缺血再灌注损伤均可导致脑组织神经细胞死亡，并致认知功能受损。最近有研究表明，脑缺血与阿尔茨海默病在发病机制上联系密切。为此，实验构建大鼠四动脉阻断全脑缺血再灌注模型，同时侧脑室注射纤维状的β淀粉样蛋白。经水迷宫实验及组织学染色结果发现，侧脑室注射β淀粉样蛋白能够进一步加重脑缺血再灌注大鼠学习与记忆能力损害和海马神经细胞的死亡。Western blot检测发现，与单纯侧脑室注射β淀粉样蛋白组和单纯脑缺血再灌注组相比，脑缺血再灌注结合脑室注射β淀粉样蛋白组脑组织tau蛋白的磷酸化水平及糖原合酶激酶3β的活性显著升高，而蛋白磷酸酶2A的活性显著降低。说明β淀粉样蛋白能够增强脑缺血再灌注引起的tau蛋白磷酸化效应，以此加重损伤认知功能。

关键词: 神经再生, 脑损伤, 脑缺血再灌注, 阿尔茨海默症, β淀粉样蛋白, 微管相关蛋白tau, 糖原合酶激酶3β, 蛋白磷酸酶2A, 磷酸化, 基金资助文章

Abstract:

Amyloid β-peptide, a major component of senile plaques in Alzheimer’s disease, has been impli-cated in neuronal cell death and cognitive impairment. Recently, studies have shown that the pathogenesis of cerebral ischemia is closely linked with Alzheimer’s disease. In this study, a rat model of global cerebral ischemia-reperfusion injury was established via occlusion of four arteries; meanwhile, fibrillar amyloid β-peptide was injected into the rat lateral ventricle. The Morris water maze test and histological staining revealed that administration of amyloid β-peptide could further aggravate impairments to learning and memory and neuronal cell death in the hippocampus of rats subjected to cerebral ischemia-reperfusion injury. Western blot showed that phosphorylation of tau protein and the activity of glycogen synthase kinase 3β were significantly stronger in cerebral is-chemia-reperfusion injury rats subjected to amyloid β-peptide administration than those undergoing cerebral ischemia-reperfusion or amyloid β-peptide administration alone. Conversely, the activity of protein phosphatase 2A was remarkably reduced in rats with cerebral ischemia-reperfusion injury following amyloid β-peptide administration. These findings suggest that amyloid β-peptide can po-tentiate tau phosphorylation induced by cerebral ischemia-reperfusion and thereby aggravate cog-nitive impairment.

Key words: neural regeneration, brain injury, cerebral ischemia-reperfusion, Alzheimer’s disease, amyloid β-peptides, tau proteins, glycogen synthase kinase 3β, protein phosphatase 2A, phosphorylation, grants-supported paper, neuroregeneration