Effect of SIRT1 overexpression in ventral tegmental area on learning,memory and synaptic structural plasticity in heroin-dependent mice
Objective To investigate the effect of silent mating type information regulation 1(SIRT1)overexpression in the ventral tegmental area(VTA)of the midbrain on learning,memory capacities and synaptic structural plasticity in heroin-dependent mice.Methods A total of 42 C57BL/6J mice were evenly divided into three groups:saline control group(SCG,n=14),heroin-dependent group(HDG,n=14)and SIRT1 overexpression in heroin-dependent group(SIRT1-OE+H,n=14).The latter two groups were established for a heroin-dependent mouse model by daily increasing injection of heroin solution.SIRT1-OE+H group were given with rAAV9-rSIRT1 adenovirus by VTA injection first.Learning and memory behaviors were monitored using conditioned place preference(CPP)and Morris water maze(MWM).On 21st day after rAAV9-rSIRT1 21 d infection,the ultrastructure of VTA synapses was observed by transmission electron microscopy.Western blot was performed to detect the expression of synaptic plasticity-related proteins in VTA.Results CCP showed that HDG group stayed longer in the drug box and had higher CPP scores than those in SCG,while SIRT1-OE+H group showed more significant changes when compared to SCG(P＜0.05).MWM localization navigation test revealed that the escape latency was prolonged in SIRT1-OE+H group on the 4th and 5th days.Spatial exploration test showed that the numbers of the crossing the platform in HDG and SIRT1-OE+H groups were increased(P＜0.05),but there were no statistical differences in the ratio of the target quadrant run to the total run and the ratio of target quadrant time to total time(P＞0.05).Transmission electron microscopy results showed that thicken postsynaptic membrane density and increased curvature of the synaptic interface in HDG and SIRT1-OE+H groups.Western blot results showed that Syn,PSD95,and Gap43 expressions were significantly enhanced in SIRT1-OE+H group when compared to SCG(P＜0.05).Conclusion SIRT1 mediates the process of heroin dependence during the time course of dependence.The mechanism may be that overexpression of SIRT1 enhances synaptic plasticity and promotes heroin-induced reward effect.However,the impact of SIRT1 on spatial learning and memory capacities is not significant.
ilent mating type information regulation 1ventral tegmental areamemorysynaptic plasticityheroin
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