Effect of ketamine on cAMP response element bidding protein phosphorylation in hippocampus of neonatal rats / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effect of ketamine on cAMP response element binding protein pbosphorylation(p-CREB)in hippocampus of neonatal rats.Methods Seventy-five 7-day old SD rats of both sexes were randomly divided into 3 groups(n=25 each)control group(group C)and 2 ketamlne groups(group K1,K2)which received 7 subcutaneous injections of ketamine 10 and 20 mg/kg respectively at 90 min intervals.The animsla were decapitated at 24 h after fwst ketamine injection.The brains were immediately removed and the hippocampi were isolated for detection of neuronal apoptosis by TUNEL.Apoptosis index wag calculated.The expression of p-CREB Wag meagured by immuno-histochemistry and the expression of BDNF mRNA and Bcl-2 mRNA was detected by RT-PCR.Cognitive function Wag agsessed using Morris water maze test at 6 weeks after first ketamine injection.Results The apoptosis index Wag significantly increased while the expression of CREB,BDNF mRNA and Bcl-2 mRNA was down-regulated in group K1 and K2 as compared with group C.The apoptosis index Wag significantly higher and the expression of p-CREB and BDNF mRNA and Bcl-2 mRNA Wag significantly lower in group K2 than in group K1.The latent period of escape was significantly longer in group K2 than in group C and K1.Conclusion Ketamine 20 mg/kg administered in neonatal rats can decrease cognitive function when they grow up by increasing neuronal apoptosis induced by down-regulatlon of the expression of p-CREB,BDNF and Bcl-2.