过表达精神分裂断裂基因1对APP/PS1转基因阿尔茨海默病小鼠突触可塑性及学习记忆能力的改善

Overexpressed DISC1 improves the synaptic plasticity,learning ability and memory of APP/PS1 transgenic alzheimer′s disease mice

目的探索精神分裂断裂基因1(DISC1)对APP/PS1转基因阿尔茨海默病(Alzheimer′s disease,AD)小鼠突触可塑性及学习记忆能力的影响。方法 Western blot比较正常人和AD患者脑组织中DISC1的表达情况;体外培养C57胎鼠神经元,分为GFP组、GFP+Aβ组、DISC1+Aβ组,激光共聚焦显微镜观察神经元树突棘。取2月龄的C57小鼠,海马注射对照病毒和DISC1过表达病毒,切脑片后Aβ处理,膜片钳技术检测长时程增强(LTP),评价突触可塑性。将C57小鼠分为WT+GFP组、TG+GFP组、TG+DISC1组三组,免疫荧光染色方法检测细胞中小鼠脑中Aβ斑块沉积;Morris水迷宫检测各组小鼠学习、记忆能力。结果与正常人比较,AD患者大脑中DISC1的表达量减少(P <0.05);与GFP组比较,GFP+Aβ组树突棘数量减少,而DISC1+Aβ组较GFP+Aβ组树突棘数量增多;Aβ处理后,小鼠脑切片的LTP减弱,而过表达DISC1后再行Aβ处理,LTP较只用Aβ处理增强;TG+DISC1组较TG+GFP组小鼠海马中的Aβ斑块减少(P <0.05),且寻找平台的时间更短、穿越平台的次数更多(P <0.05)。结论过表达DISC1对APP/PS1转基因AD小鼠突触可塑性具有保护作用并能够改善其学习记忆能力。

Objective To explore the effect of DISC1 on the synaptic plasticity,learning and memory ability of APP/PS1 transgenic alzheimer′s disease mice.Methods Western blot was used to detect the expression of DISC1 in the brain tissues between normal people and AD patients.C57BL/6J fetal mouse neurons were cultured in vitro and divided into GFP group,GFP+Aβgroup and DISC1+Aβgroup.Laser confocal microscope was used to observe neuron dendritic spines.Two⁃month⁃old C57BL/6J mice were injected into the hippocampus with GFP virus or DISC1⁃overexpressed virus,and then brains were sliced for Aβtreatment.After Aβtreatment,patch clamp technique was used to detect long⁃term potentiation(LTP)of each group to evaluate synaptic plasticity.C57BL/6J mice were divided into WT+GFP group,TG+GFP group,and TG+DISC1 group.Immol/Lunofluorescence stain⁃ing was used to detect Aβplaque deposition in the brain and Morris water maze to detect the learning and memory abilities of mice in each group.Results Compared with the none⁃AD people,the expression of DISC1 in the brain of AD patients decreased(P<0.05).Compared with the GFP group,the number of dendritic spines in the GFP+Aβgroup decreased,while the number of dendritic spines increased in the DISC1 Aβgroup compared to the GFP Aβgroup.After Aβtreatment,LTP of mouse brain slices weakened compared with the control group,and with overexpressed DISC1,LTP was enhanced compared with Aβtreatment only.The number of Aβplaques in the hippocampus of TG+DISC1 group was significantly smaller than that in TG+GFP group(P<0.05).In Morris test,the time to find the platform was significantly shorter and the number of times to cross the platform was larger(P<0.05).Conclusion Overexpressed DISC1 can protect the synaptic plasticity of APP/PS1 transgenic AD mice and improve its learning ability and memory.