Effect of endocannabinoids pretreatment on the expression of AMPA receptor GluR2 subunit in the hippocampal pyramidal neurons of mouse

LIU Zhaoyu; GAO Yang; SUN Sisi; CHEN Shaoyang; WANG Qiang

Abstract：Objective Whether endocannabinoids pretreatment affects the expression of the α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor 2 subunit (GluR2) in mice after global cerebral ischemia-reperfusion (I/R) injury and its mechanism are investigated.Methods Adult male C57BL/6 mice were randomly divided into five groups:sham group, I/R group, 2-arachidonoyl glycerol (2-AG) group, cannabinoid 1 receptor (CB1R) antagonist(AM251)+2-AG group and vehicle group.The mice in 2-AG group were injected 2-AG with a dose of 5 mg/kg intraperitoneally.AM251 was injected intraperitoneally with a dose of 1 mg/kg 30 min before pretreatment.2-AG was administered in AM251+2-AG group mice with a dose of 5 mg/kg.A total of 0.1 ml Dimethylsulfoxide (DMSO) (the solvent of 2-AG or AM251) was injected intraperitoneally in vehicle group mice. Global cerebral I/R was induced at 30 min after preconditioning by occlusion of bilateral common carotid artery for 20 min and then followed by reperfusion.Immunofluorescence and Western blot were employed to detect the expression of GluR2 in the hippocampus.Results The AMPA receptor GluR2 subunit was highly expressed in the pyramidal cell layers of hippocampal CA1.Two hours after reperfusion, global cerebral ischemia induced a marked reduction in GluR2 expression in the pyramidal neurons (P<0.05).In 2-AG group, hippocampal neuronal GluR2 expression was significantly up-regulated compared with that of I/R group (P<0.05).The GluR2 expression decreased in the AM251 +2-AG group compared with that in 2-AG group ( P <0.05 ).Conclusion Endocannabinoids preconditioning increases the expression of hippocampal neuronal AMPA receptor GluR2 via CB1R after global cerebral ischemia.