【摘要】 目的:携带pEGFP/A2M(FP6)的神经干细胞(NSCs)定向移植到APP/PS1双转基因AD小鼠海马内,观察移植细胞的分化、迁移,脑内Aβ沉积的变化,以及对AD小鼠学习记忆功能的影响。方法:APP/PS1转基因AD小鼠分为假手术(SO)组、人工脑脊液(ACSF)组、转染pEGFP的NSCs(pEGFP-NSCs)组及转染pEGFP/A2M(FP6)的NSCs(pEGFP/A2M(FP6)-NSCs)组,移植物小鼠海马CA1区定位注射,水迷宫实验检测小鼠认知功能,免疫组化观察小鼠脑内移植细胞的分化、迁移及Aβ病理变化。结果:pEGFP/A2M(FP6)-NSCs组和pEGFP-NSCs组转基因小鼠逃避潜伏期较SO组及ACSF组显著缩短(P<0.05);pEGFP/A2M(FP6)-NSCs组转基因小鼠逃避潜伏期较pEGFP-NSCs组缩短(P<0.05)。pEGFP/A2M(FP6)-NSCs组和pEGFP-NSCs组转基因小鼠海马及皮质内,部分Aβ染色阳性斑块周围可见表达EGFP的移植细胞。pEGFP/A2M(FP6)-NSCs组转基因小鼠额叶、海马区域,Aβ染色阳性斑块数量和平均面积均较其他3组显著减少(P<0.05)。移植的NSCs,部分细胞Nestin染色呈阳性,部分细胞GFAP染色呈阳性,少数细胞MAP-2染色呈阳性。结论:移植pEGFP/A2M(FP6)NSCs到APP/PS1双转基因AD小鼠海马,可减少AD小鼠脑内Aβ斑块沉积,部分移植的NSCs分化为神经元及星形胶质细胞,小鼠的学习记忆功能显著改善。更多还原

【Abstract】 Objective: To observe the migration and differentiation of pEGFP/A2M(FP6) transfected neural stem cells(NSCs),the deposits of Aβn the brain and the change of learning and memory ability of APP/PS1 double transgenic mice of Alzheimer’s Disease(AD) after the NSCs were transplanted into the hippocampus.Methods: APP/PS1 transgenic AD mice were randomly divided into four groups: sham operated(SO) group, artificial cerebrospinal fluid(ACSF) group,transfected pEGFP neural stem cell(pEGFP-NSCs) group and transfected pEGFP/A2M(FP6) neural stem cell(pEGFP/A2M(FP6)-NSCs) group.The ACSF,pEGFP-NSCs or pEGFP/A2M(FP6)-NSCs were transplanted into the CA1 region of the hippocampus of the mice.The learning and memory ability of the mice were assessed with Mirror water maze test.The migration and differentiation of pEGFP/A2M(FP6) transfected NSCs and the deposits of Aβn the brain of the mice were observed by immunohistochemistry.Results: The latencies of pEGFP/A2M(FP6)-NSCs group and pEGFP-NSCs group were significantly shorter than that in the SO group and ASCF group(P<0.05).The latency of pEGFP/A2M(FP6)-NSCs group was shorter than that in the pEGFP-NSCs group(P<0.05).Anti-Aβetection showed Aβeposits in the hippocampus and cortex of pEGFP/A2M(FP6)-NSCs group and pEGFP-NSCs group were surrounded by transplanted NSCs.The amount and average size of Aβeposits in the hippocampus and cortex of pEGFP/A2M(FP6)-NSCs group were reduced markedly,compared with the other three groups(P<0.05).The expression of Nestin was detecte after transplantation.Immunofluorescent detection indicated that majority of transplanted cells expressed GFAP while only a few cells expressed MAP-2.Conclusion: Transplantation of pEGFP/A2M(FP6)-NSCs into the hippocampal region of APP/PS1 double transgenic AD mice could reduce the Aβeposits and promote the learning and memory ability.Partial transplanted NSCs will differentiate into neurons or astrocytes.更多还原