丰富环境通过激活Wnt/β-catenin信号通路促进脑缺血小鼠海马区的突触重塑

Enriched environments promote synaptic remodeling in the hippocampus by activating the Wnt/p-catenin signaling pathway

目的探讨丰富环境饲养促进脑缺血小鼠海马区突触重塑的作用机制。方法清洁级成年雄性小鼠(C57BL/6)60只,按随机数字表法选取16只设为假手术组,剩余44只接受永久性左侧大脑中动脉栓塞(pMCAO)手术。将造模成功的32只小鼠随机分为标准饲养组和丰富环境组,每组16只。术后3 d行丰富环境干预,假手术组和标准环境组置于标准环境鼠笼中饲养,丰富环境组置于丰富环境鼠笼中饲养,持续干预28 d;干预28 d后,采用透射电镜技术及蛋白免疫印迹检测技术,分别检测和观察分析3组小鼠海马CA3区的突触数量以及海马区Wnt7a、Dvl1、β-catenin、突触素、PSD-95蛋白表达水平的变化。结果与标准环境组相比,丰富环境组海马区突触素、PSD-95、Wnt7a、Dvl1、β-catenin的蛋白表达水平显著升高,与标准饲养组比较,差异均有统计学意义(P<0.05)。丰富环境组海马CA3区的突触数量亦明显高于标准饲养组(P<0.05)。结论丰富环境可以激活脑缺血小鼠海马区Wnt7a-β-catenin-Dvl1信号通路,从而促进脑缺血小鼠海马区突触重塑。

Objective To explore how an enriched environment promotes synaptic remodeling in the hippocampus after cerebral ischemia.Methods Among 60 clean,adult,male C57BL/6 mice,16 were randomly selected into a sham operation group,while the remaining 44 underwent permanent left middle cerebral artery embolization.The 32 mice with successful modeling were randomly divided into a normal environment group and an enriched environment group,each of 16.The enriched environment group lived in an enriched environment for 28 days,while the other two groups were raised in normal conditions.The number of synapses in the CA3 area of the hippocampus was then measured using transmission electron microscopy,and the expression of Wnt7a,Dvl1,β-catenin,synaptophysin(SYN)and PSD-95 in the hippocampus were measured using western blotting.Results Compared with the normal environment group,the average protein expression levels of Wnt7a,Dvl1,β-catenin,SYN and PSD-95 were all significantly higher in the enriched environment group.The number of synapses in the CA3 region of the enriched environment group was also significantly higher than in the normal environment group.Conclusion An enriched environment can activate the Wnt7a-β-catenin-Dvl1 signaling pathway in the hippocampus after cerebral ischemia to promote synaptic remodeling,at least in mice.