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Wnt-5a 阻断 Abeta 寡聚体诱导的海马神经元谷氨酸能传递抑制。

Wnt-5a occludes Abeta oligomer-induced depression of glutamatergic transmission in hippocampal neurons.

机构信息

Centro de Envejecimiento y Regeneración (CARE), Centro de Regulación Celular y Patología "Joaquín V, Luco" (CRCP), MIFAB, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

出版信息

Mol Neurodegener. 2010 Jan 18;5:3. doi: 10.1186/1750-1326-5-3.

DOI:10.1186/1750-1326-5-3
PMID:20205789
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2823745/
Abstract

BACKGROUND

Soluble amyloid-beta (Abeta;) oligomers have been recognized to be early and key intermediates in Alzheimer's disease (AD)-related synaptic dysfunction. Abeta oligomers block hippocampal long-term potentiation (LTP) and impair rodent spatial memory. Wnt signaling plays an important role in neural development, including synaptic differentiation.

RESULTS

We report here that the Wnt signaling activation prevents the synaptic damage triggered by Abeta oligomers. Electrophysiological analysis of Schaffer collaterals-CA1 glutamatergic synaptic transmission in hippocampal slices indicates that Wnt-5a increases the amplitude of field excitatory postsynaptic potentials (fEPSP) and both AMPA and NMDA components of the excitatory postsynaptic currents (EPSCs), without modifying the paired pulse facilitation (PPF). Conversely, in the presence of Abeta oligomers the fEPSP and EPSCs amplitude decreased without modification of the PPF, while the postsynaptic scaffold protein (PSD-95) decreased as well. Co-perfusion of hippocampal slices with Wnt-5a and Abeta oligomers occludes against the synaptic depression of EPSCs as well as the reduction of PSD-95 clusters induced by Abeta oligomers in neuronal cultures. Taken together these results indicate that Wnt-5a and Abeta oligomers inversely modulate postsynaptic components.

CONCLUSION

These results indicate that post-synaptic damage induced by Abeta oligomers in hippocampal neurons is prevented by non-canonical Wnt pathway activation.

摘要

背景

可溶性淀粉样β（Abeta;）寡聚体已被认为是阿尔茨海默病（AD）相关突触功能障碍的早期和关键中间产物。Abeta 寡聚体阻断海马长时程增强（LTP）并损害啮齿动物的空间记忆。Wnt 信号在神经发育中发挥重要作用，包括突触分化。

结果

我们在此报告，Wnt 信号的激活可防止 Abeta 寡聚体引发的突触损伤。海马切片中 Schaffer 侧支-CA1 谷氨酸能突触传递的电生理分析表明，Wnt-5a 增加了场兴奋性突触后电位（fEPSP）的幅度，以及兴奋性突触后电流（EPSCs）的 AMPA 和 NMDA 成分，而不改变成对脉冲易化（PPF）。相反，在 Abeta 寡聚体存在的情况下，fEPSP 和 EPSCs 的幅度降低，而 PPF 没有改变，同时突触后支架蛋白（PSD-95）也减少。在海马切片中共同灌流 Wnt-5a 和 Abeta 寡聚体可阻止 EPSCs 的突触抑制以及神经元培养物中 Abeta 寡聚体诱导的 PSD-95 簇减少。综上所述，这些结果表明 Wnt-5a 和 Abeta 寡聚体反向调节突触后成分。

结论

这些结果表明，Abeta 寡聚体在海马神经元中引起的突触后损伤可通过非经典 Wnt 途径的激活来预防。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe8/2823745/2192547957fd/1750-1326-5-3-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe8/2823745/5dcbcee75c20/1750-1326-5-3-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe8/2823745/96d55ff23ba1/1750-1326-5-3-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe8/2823745/013843b048cf/1750-1326-5-3-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe8/2823745/4f091ac0eb58/1750-1326-5-3-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe8/2823745/bc0976a96b34/1750-1326-5-3-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe8/2823745/2192547957fd/1750-1326-5-3-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe8/2823745/5dcbcee75c20/1750-1326-5-3-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe8/2823745/96d55ff23ba1/1750-1326-5-3-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe8/2823745/013843b048cf/1750-1326-5-3-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe8/2823745/4f091ac0eb58/1750-1326-5-3-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe8/2823745/bc0976a96b34/1750-1326-5-3-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe8/2823745/2192547957fd/1750-1326-5-3-6.jpg

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2
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J Biol Chem. 2009 Jun 5;284(23):15857-66. doi: 10.1074/jbc.M808986200. Epub 2009 Mar 30.
3
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Nat Metab. 2024 Mar;6(3):531-549. doi: 10.1038/s42255-024-00989-x. Epub 2024 Feb 26.
4
Secreted Glycoproteins That Regulate Synaptic Function: the Dispatchers in the Central Nervous System.分泌型糖蛋白在突触功能调节中的作用：中枢神经系统的调度员。
Mol Neurobiol. 2024 May;61(5):2719-2727. doi: 10.1007/s12035-023-03731-y. Epub 2023 Nov 4.
5
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6
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5
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6
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7
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8
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9
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10
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