缺血损伤后突触后膜GluR2含量变化及机制

Changes of GluR2 on post-synaptic membrane and its mechanisms after ischemic insult

目的 探讨缺血损伤后突触后膜谷氨酸受体 2 (glutamatereceptor 2 ,GluR2 )含量变化、机制及其在神经元延迟性死亡中的作用。方法 采用PI染色、比色分析和双重免疫荧光技术定量观察神经元死亡、膜表面及突触GluR2含量变化及途径。结果 缺血损伤神经元死亡数量明显增加 ;膜表面GluR2总量、含GluR2的突触数目以及突触部位GluR2含量都明显降低 (P <0 0 5 ) ,而胞内GluR2含量则显著增加 ,采用高渗糖预处理阻断内吞过程可显著抑制膜表面GluR2的降低过程。结论 缺氧损伤后膜GluR2内吞过程增强 ,导致了膜表面GluR2含量降低 ,缺乏GluR2的AMPA受体增加 ,进而介导了Ca2 + 的快速内流 ,引起神经元延迟性死亡。

Objective To explore the changes of glutamate receptor (GluR2) on the post-synaptic membrane, the potential mechanisms, and the effects on the delayed neuron death after oxygen-glucose deprivation (OGD). Methods The neuron death, GluR2 contents on the membrane, and the post-synaptic membrane and the paths were quantitatively observed by PI staining, colorimetric assay, and double immuno-fluorescence labeling. Results The number of delayed death neuron increased significantly after OGD. The total surface GluR2, the number of synapses with GluR2, and the quantity of GluR2 in synapse were marked lower than those in the control group (P<0.05). On the contrary, the intracellular GluR2 content increased significantly. The pretreatment of hypertonic sucrose, which would block the endocytosis, inhibited the decrease of GluR2 effectively. Conclusion OGD would accelerate the endocytosis of GluR2 and induce decreased GluR2 content on the postsynaptic membrane, so the number of GluR2-lacking amino-3-hydroxy-5 methylisoxazole-4-propionic acid (AMPA) receptors may increase, which may mediate the influx of Ca 2+ and result in delayed neuron death.