β-amyloid oligomers affect the structure and function of the postsynaptic region:: Role of the Wnt signaling pathway
β-amyloid oligomers affect the structure and function of the postsynaptic region:: Role of the Wnt signaling pathway
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DOI：
10.1159/000113687
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发表时间：
2008-01-01
影响因子：
3
通讯作者：
Inestrosa, Nibaldo C.
中科院分区：
文献类型：
--
作者：
Dinarnarca, Margarita C.;Colombres, Marcela;Inestrosa, Nibaldo C.
背景阿尔茨海默病（Alzheimer's disease，AD）是老年人中最常见的神经退行性疾病。突触功能障碍是AD的早期表现。P-淀粉样肽（A β）影响突触的细胞机制仍不清楚。在培养的大鼠海马神经元中，A β寡聚体靶向突触，这表明它们在突触的调节中起关键作用。目的：本工作的目的是研究A β寡聚体对中枢突触的影响以及Wnt信号通路在预防A β效应中的可能作用。方法：采用大鼠海马神经元，免疫荧光和westernblot方法检测突触蛋白的表达.结果：A β寡聚体诱导突触后密度蛋白95（PSD-95）和NMDA谷氨酸受体减少。我们发现，Wnt-5a，一种非经典的Wnt配体，阻止了谷氨酸受体和PSD-95中A β寡聚体引发的减少。结论：总之，我们的研究结果表明，A β寡聚体通过在不同水平上影响突触后区域来降低突触反应。Wnt信号传导激活防止A β诱导的突触损伤，这提高了治疗AD中观察到的突触变化的新治疗干预的可能性。版权所有（c）2008 S. Karger AG，巴塞尔。
Background. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the growing population of elderly people. Synaptic dysfunction is an early manifestation of AD. The cellular mechanism by which P-amyloid peptide (A beta) affects synapses remains unclear. A beta oligomers target synapses in cultured rat hippocampal neurons suggesting that they play a key role in the regulation of synapses. Objective: The aim of this work is to study the effect of A beta oligomers on the central synapses and the possible role of the Wnt signaling pathway in preventing the A beta effects. Methods: We used rat hippocampal neurons, immunofluorescence and western blot procedures to detect synaptic proteins. Results: A beta oligomers induced a reduction of the postsynaptic density protein 95 (PSD-95) and the NMDA glutamate receptors. We found that Wnt-5a, a noncanonical Wnt ligand, prevents the decrease triggered by A beta oligomers in the glutamate receptor and PSD-95. Conclusion: Altogether, our results suggest that A beta oligomers decrease the synaptic responses by affecting the postsynaptic region at different levels. The Wnt signaling activation prevents synaptic damage induced by A beta, which raises the possibility of a new therapeutic intervention for the treatment of synaptic changes observed in AD. Copyright (c) 2008 S. Karger AG, Basel.