NMDA受体在β-淀粉样蛋白引起海马神经元突触蛋白改变中的作用

Effects of NMDA receptors on amyloid-beta induced alteration of synaptic proteins in hippocampal neurons

为了研究NMDA受体活性对Aβ引发的海马神经元突触蛋白表达变化的影响,本文运用免疫细胞化学方法检测不同浓度NMDA受体激动剂以及拮抗剂对Aβ诱导的海马神经元突触蛋白变化的影响。结果显示:NMDA可浓度依赖性地缓解Aβ25-35引起的突触蛋白synaptophysin与PSD-95的减少。抑制突触内NMDA受体,NMDA缓解Aβ减少突触蛋白的作用减弱;抑制突触外NMDA受体,对抗Aβ的作用无显著变化。本研究结果提示NMDA受体活性改变影响Aβ诱导的突触蛋白减少,突触内NMDA受体激活可对抗Aβ的毒性作用。突触内NMDA受体活性减弱可能在谷氨酸兴奋毒性中发挥作用。

To investigate the effects of NMDA receptors on the Aβ-induced alteration of synaptic proteins, we applied immunocytochemistry to investigate the changes of the expression of synaptic proteins in primary hippocampal neurons which were exposed to Aβ25.35 after the treatment of different concentrations of NMDA receptor agonist and synaptic or extrasynaptic NMDA receptor antagonist. The results showed that NMDA prevented Aβ25.35 to reduce the expression of synaptophysin and PSD-95 in a dose-dependent manner. When synaptic NMDA receptors were blocked, the effect that NMDA prevented Aβ-mediated downregulation of synaptic protein was attenuated. On the other hand, blockade of extrasynaptic NMDA receptor did not influence the effect of Aβ at all. These results thus suggest that Aβ-induced downregulation of synaptic proteins depends on NMDA receptor activity, and the activation of synaptic NMDA receptors opposed the neurotoxicity of Aβ. The decrease of synaptic NMDA receptors activity may play a role in glutamate-mediated excitotoxicity.