Dinamarca Margarita C, Colombres Marcela, Cerpa Waldo, Bonansco Christian, Inestrosa Nibaldo C
Centro de Regulación Celular y Patología Joaquín V. Luco, MIFAB, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Neurodegener Dis. 2008;5(3-4):149-52. doi: 10.1159/000113687. Epub 2008 Mar 6.
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 beta-amyloid peptide (Abeta) affects synapses remains unclear. Abeta oligomers target synapses in cultured rat hippocampal neurons suggesting that they play a key role in the regulation of synapses.
The aim of this work is to study the effect of Abeta oligomers on the central synapses and the possible role of the Wnt signaling pathway in preventing the Abeta effects.
We used rat hippocampal neurons, immunofluorescence and western blot procedures to detect synaptic proteins.
Abeta 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 Abeta oligomers in the glutamate receptor and PSD-95.
Altogether, our results suggest that Abeta oligomers decrease the synaptic responses by affecting the postsynaptic region at different levels. The Wnt signaling activation prevents synaptic damage induced by Abeta, which raises the possibility of a new therapeutic intervention for the treatment of synaptic changes observed in AD.
在不断增长的老年人群中，阿尔茨海默病（AD）是最常见的神经退行性疾病。突触功能障碍是AD的早期表现。β-淀粉样肽（Aβ）影响突触的细胞机制尚不清楚。Aβ寡聚体靶向培养的大鼠海马神经元中的突触，表明它们在突触调节中起关键作用。
本研究旨在探讨Aβ寡聚体对中枢突触的影响以及Wnt信号通路在预防Aβ效应中的可能作用。
我们使用大鼠海马神经元、免疫荧光和蛋白质印迹法检测突触蛋白。
Aβ寡聚体导致突触后致密蛋白95（PSD-95）和NMDA谷氨酸受体减少。我们发现，非经典Wnt配体Wnt-5a可防止Aβ寡聚体引起的谷氨酸受体和PSD-95减少。
总之，我们的结果表明，Aβ寡聚体通过在不同水平影响突触后区域来降低突触反应。Wnt信号激活可预防Aβ诱导的突触损伤，这为治疗AD中观察到的突触变化提供了一种新的治疗干预可能性。
