Effect And Mechanism Of AE-624 On Cognitive Behavior Of Mice Induced By Streptozotocin Intracerebroventricular Injection

Objective: To investigate the effect of AE-624 on PC12 cells injury induced by LPS.To investigate the effect and mechanism of AE-624 on cognitive behavior of mice induced by streptozotocin intracerebroventricular injection.Methods:(1)PC12 cells were processed with 200?g/mL LPS to establish the cell injury model,and 5,10,20,40,60,80,100?g/m L AE-624 was used to antagonize against its effect.The cell survival rate was detected with MTT.(2)Kunming mice or BALB/c mice were randomly divided into control group,model group,positive control group(Donepezil group),AE-624 low,medium and high dose groups.Every group was induced by STZ intracerebroventricular(i.c.v.)injection(30?g/?L,5?L)except for control group(PBS).Then mice were treated by different concentrations(5,15,45mg/kg)of AE-624 for 15 ds.The cognitive behavior of mice were detected by locomotor activity,novel object recognition,zero maze test,Morris water maze test,the affect of synaptic plasticity was observed by LTP,Then the level of SOD and malondialdehyde(MDA)in serum and brain tissue of the mice were detected in each group.the affect of neurons was observed by Nissl staining.Results:(1)Compared with the model group,AE-624 could significantly improve the the PC12 cell survival rate(P<0.05 or P<0.005),and had protective effects on PC12 cells injured by LPS.(2)Compared with model group,AE-624 could improve the cognitive abilities and LTP : their spontaneous motor activity increased(P<0.05),the new object recognition priority index increased(P<0.05),Time in open section was increased significantly(P<0.05 or P<0.01)in the zero maze test,escape latency decreased significantly in the Morris(P<0.01 or P<0.005),PS-wave growth was significantly higher than the model group(P<0.05).Compared with control group,SOD activity revealed a significant decrease(P<0.05)and MDA content exhibited a significant increase in serum and brain tissue in model mice(P<0.001).Compared with model group,SOD activity in serum and brain tissue exhibited a significant increase and MDA content decreased in AE-624 treatment group(P<0.05 or P<0.001).Compared with the control group,the number of neurons in the model group was decreased significantly(P<0.01).compared with the model group,AE-624 could significantly increase the number of neurons in hippocampus of mice(P<0.05),AE-624 has a significant protective effect on hippocampal neurons.Conclusion:(1)AE-624 has protective effects on PC12 cells injured by LPS.(2)AE-624 has significantly protective effects on brain damage of mice induced by streptozotocin(STZ),and it's protective mechanism probably related to antioxidation?anti-apoptosis and increasing LTP in hippocampus of mice PP-DG region and improving synaptic plasticity.