Changed Clathrin Regulatory Proteins in the Brains of Alzheimer's Disease Patients and Animal Models
Changed Clathrin Regulatory Proteins in the Brains of Alzheimer's Disease Patients and Animal Models
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DOI：
10.3233/jad-2010-100162
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Guan, Zhi-Zhong
中科院分区：
文献类型：
--
作者：
Cao, Ying;Xiao, Yan;Guan, Zhi-Zhong
研究中，研究了阿尔茨海默病（AD）患者、携带瑞典突变淀粉样β蛋白前体（AβPP）670/671（AβPPSWE）的转基因小鼠以及大鼠的多个脑区中网格蛋白调节蛋白dynamin I、AP180和突触小泡蛋白突触素的表达情况。 双侧海马注射淀粉样β肽(Aβ)(1-42)，分别采用免疫组织化学、尼氏染色、Western blotting和Real-time PCR进行检测。采用Morris水迷宫实验评价大鼠的空间学习记忆能力，采用FM1-43荧光成像检测培养的大鼠海马神经元的内吞能力。与对照组相比，AD 患者和 A beta PPSWE 小鼠的动力蛋白 I、AP180 和突触素蛋白水平显着降低。与对照组相比，注射 A beta(1-42) 的大鼠发现动力 I 和突触素的蛋白质和 mRNA 水平明显下降，学习和空间记忆能力受损。此外，还发现Aβ沉积在Aβ(1-42)注射部位周围的海马中，并且神经元中尼氏体数量减少。此外，在用 A beta(1-42) 处理的受刺激海马神经元中检测到突触小泡内吞作用中断和动力 I 蛋白减少。这些发现意味着 AD 病理过程中网格蛋白介导的内吞作用发生故障，这可能与 AD 相关认知缺陷的机制有关。
In the study, the expression of clathrin regulatory proteins dynamin I, AP180, and synaptic vesicle protein synaptophysin in multiple brain regions of the patients with Alzheimer's disease (AD), the transgenic mice carrying the Swedish mutation of amyloid-beta protein precursor (A beta PP)670/671 (A beta PPSWE), and the rats injected by bilateral hippocampus with amyloid-beta peptide (A beta)(1-42) were examined by immunohistochemistry and Nissl staining, Western blotting, and Real-time PCR, respectively. Spatial learning and memory of the rats were evaluated by Morris Water Maze test, and the ability of endocytosis in the cultured rat hippocampal neurons was detected by FM1-43 fluorescence imaging. Significant decreases in protein levels of dynamin I, AP180, and synaptophysin were observed in both AD patients and mice with A beta PPSWE as compared to controls. Obvious declines of dynamin I and synaptophysin at protein and mRNA levels and impaired learning and spatial memory ability were found in the rats injected with A beta(1-42) as compared to controls. In addition, deposits of A beta localized in the hippocampus around the sites of A beta(1-42) injection and the decreased numbers of Nissl bodies in neurons were found. Moreover, the disrupted synaptic vesicle endocytosis and decreased dynamin I protein were detected in stimulated hippocampal neurons treated with A beta(1-42). These findings imply a malfunctioning clathrin-mediated endocytosis during AD pathological processes, which might be relevant to the mechanism underlying the cognitive deficit associated with AD.