Mechanism And Antidepression Effects Of Ketamine By Regulation The Activation Of Microglia

[Objective] Ketamine is a kind of potential antidepressant drugs In this research,we establish the kunming mice depression models by the method of chronic restraint stress(CRS), and explored the mechanism and the role of ketamine antidepressant.[Method] Forty-eight healthy male adult kunming mice were equally randomized into three groups,model ketamine group, model control group,and blank control group,CRS were used to establish the mice depression model in model ketamine group and model control group,and the blank control group was not treated.In the 23 and 24 days,the three groups animals were forced swimming test and sucrose preference test to observe the behavior changes, the protein expression of IBA-1, CD11 and P2X7 was detected by immunohistochemistry, and the content of corticosterone in animal blood was tested by ELISA.[Result] The forced swimming time was remarkably longer in the model control group(53.79 s ±6.01s)than the blank control group( 27.58 s ±3.68s)(p<0.05),and the time was remarkably shorter in the model ket group(26.75 s ±3.02s) than the model control group(P <0.05).The 0-24 h sucrose consumption was markedlyhigher in the model control group(38.96 ±6.16) than the blank control group(77.29±8.87)(P<0.05), and the sucrose consumption was remarkably shorter in the model ket group(74.16 ±2.61) than the model control group(P<0.05).The 24h-48 h sucrose consumption was markedly higher in the model control group(37.99 ±5.85) than the blank control group(79.92±5.52)(P<0.05), and the sucrose consumption was remarkably shorter in the model ket group(80.90 ±3.88) than the model control group(P<0.05).The ELISA result show that the content of corticosterone in animal blood was remarkably higher in the model control group( 725.78±23.62ng/ml) than in the blank control group( 162.32±23.45ng/ml), and the content of corticosterone model was remarkably lower in model ket group(362.73±28.52ng/ml) than the model control group((P<0.05),and has statistical significance with the blank control group((P<0.05). The average number of activated microglia per 40 x field of vision was markedly higher in the model control group(18.61±2.47) than the blank control group(6.15±1.91)(P<0.05), and the number was significantly less in the model ket group(9.52±1.36) than the model control group(P<0.05); The CD11 b immunohistochemical results showed that in model control group CD11 b positive expression was observed in the hippocampus, and the other two groups of expression is low; The P2X7 protein express was markedly higher in the model control group than the blank control group(P<0.05),and the express was significantly lower in the model ket group than the model control group(P<0.05). [Conclusion] Ketamine can inhibit the activation of microglia in hippocampus in depression,and the ketamine down-regulation the express expression of P2X7 which caused by the chronic stress, may be one of ketamine antidepressant mechanism.