NMDA受体的活化调节原代皮层神经元的Wnt/β-catenin信号通路

NMDA Receptor Activation Regulates Wnt/β-catenin Signaling Pathway in Primary Cortical Neurons

经典的Wnt/β-catenin信号通路在中枢神经系统突触形成和功能中发挥重要的调节作用。作为兴奋性神经递质的谷氨酸,与其受体结合,参与许多信号调节活动。为了探讨NMDA受体活化对Wnt/β-catenin信号通路的作用,该文利用18 d的C57小鼠胚胎培养皮层神经元(离体10 d),用10μmol/L谷氨酸钠(monosodium glutamate,MSG)和50μmol/L N-甲基-D-天冬氨酸(NMDA)处理细胞,通过蛋白免疫印迹技术或者细胞免疫荧光染色分析Wnt/β-catenin信号通路关键成员。结果发现,NMDA受体的活化能使GSK-3β的Ser9位磷酸化水平增加,活性被抑制,胞浆内β-catenin蛋白降解减少,入核增加,激活下游基因表达。这些结果提示,NMDA受体激活能够上调Wnt/β-catenin信号通路。

Wnt signaling has a key role in regulation of synaptic formation and function in the brain.Glutamate,which is the mainly excitatory transmitter,binds the glutamic acid receptor to regulate the activity of many signaling pathways.To determine the effect of NMDA receptor activation on Wnt/β-catenin signaling,primary cortical C57 mouse neurons were treated with 10 μmol/L MSG and 50 μmol/L NMDA and the components of Wnt/ β-catenin signaling were analyzed by Western blot or immunofluorescent experiments.We found that NMDAreceptor activation not only increased the p-Ser9-GSK-3β to inhibit its activity but also caused an increase of intracellular β-catenin and induced its translocation into nuclei,thereby up-regulated the downstream gene expression.These results suggest that NMDA receptors activation up-regulates Wnt/β-catenin signaling in primary cortical cultured neurons.