The aging brain is associated with reduced cell surface expression of N-methyl-d-aspartate receptors (NMDARs), but the mechanism remains poorly understood. In the present study, we showed that in the striatum and hippocampus but not the cerebellum and parietal cortex, levels of α-synuclein monomers and oligomers increased with age, which correlated negatively with the expression of GluN1, and positively with the expression of total Rab5B. The oligomer-α-synuclein exhibited a stronger correlation with the expression of surface GluN1 and total Rab5B. In MES23.5 cells, the monomer- or oligomer-α-synuclein were shown to increase in a manner dependent on the concentrations of the added monomers and oligomers. Again, the oligomer-α-synuclein showed more potent effects than the monomer-α-synuclein on surface GluN1 and total Rab5B expression. Accordingly, the oligomer-treated cells showed a greater reduction in NMDA-evoked Ca2+ influx than the monomer-treated cells, which was largely inhibited by pistop2, a clathrin inhibitor. These results suggest that the age-dependent accumulation of α-synuclein monomers and oligomers differentially contributes to the reduction in surface NMDAR expression in selective brain regions.

中文翻译：

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α-突触核蛋白差异性地降低老化人脑中 NMDA 受体的表面表达

大脑老化与 N-甲基-d-天冬氨酸受体 (NMDARs) 的细胞表面表达减少有关，但其机制仍知之甚少。在本研究中，我们发现在纹状体和海马中，而不是小脑和顶叶皮层中，α-突触核蛋白单体和寡聚体的水平随着年龄的增长而增加，这与 GluN1 的表达呈负相关，与总 Rab5B 的表达呈正相关. 寡聚体-α-突触核蛋白与表面 GluN1 和总 Rab5B 的表达表现出更强的相关性。在 MES23.5 细胞中，单体或寡聚体-α-突触核蛋白的增加方式取决于添加的单体和寡聚体的浓度。同样，寡聚体-α-突触核蛋白在表面 GluN1 和总 Rab5B 表达上显示出比单体-α-突触核蛋白更有效的影响。因此，与单体处理的细胞相比，寡聚体处理的细胞显示出 NMDA 诱发的 Ca2+ 流入减少更多，这在很大程度上受到网格蛋白抑制剂 pistop2 的抑制。这些结果表明，α-突触核蛋白单体和寡聚体的年龄依赖性积累对选择性大脑区域表面 NMDAR 表达的降低有不同的贡献。