神经干细胞移植对APP/PS1小鼠突触形成的影响
Effects of transplanted neural stem cells on synaptogenesis in APP/PS1 mice
目的 探讨神经干细胞 (NSCs) 移植对阿尔茨海默病 (AD) 小鼠突触形成的影响.方法 9月龄20只APP/PS1双转基因AD小鼠随机分为2组,每组10只,一组进行NSCs移植,即NSC组,另一组给予等量磷酸盐缓冲液 (PBS) 作为阴性对照组 (PBS组),移植部位为双侧海马区,10只野生型小鼠作为阳性对照组 (WT组).移植8周后采用荧光免疫组化法和Western印迹检测AD小鼠海马区突触素 (SYN) 和生长相关蛋白-43 (GAP-43) 表达的变化;透射电镜观察移植区突触的形态和数量.结果 (1)荧光免疫组化显示NSCs移植分化的神经元高表达SYN和GAP-43蛋白;(2) Western印迹显示NSC组小鼠海马区SYN、GAP-43表达明显增加,高于PBS组 (F=58.367,P<0.01;F= 75.296,P<0.01),SYN表达与WT组小鼠相比较差异无统计学意义(P>0.05),但是NSC组小鼠GAP-43表达高于WT组 (P<0.01);(3)超微结构显示NSC组海马区突触数量增加 (12.1±2.1),多于PBS组 (6.6±1.8) (F= 15.981,P <0.01),与WT组 (11.0±1.4) 相比较差异无统计学意义 (P>0.05).结论 NSCs移植分化的神经元通过增加突触素、GAP-43表达来增加突触的数量,进而建立新的突触连接来改善AD小鼠的症状.
更多Objective To explore the effects of transplanted neural stem cells (NSCs) on synaptogenesis in an Alzheimer′ disease (AD) murine model and related mechanism. Methods Twenty 9-month-old APP/PS1 double transgenic mice were randomly divided into 2 groups. One group received NSCs transplantation (NSC group) in bilateral hippocampi while another group received an equal volume of 0.01 mol/L phosphate buffer saline (PBS group) as a negative control group. Ten wild-type mice were selected as the positive control group (WT group) without any treatment. After 8-week transplantation, the expressions of synaptophysin (SYN) and growth associated protein-43 (GAP-43) proteins in hippocampal areas were analyzed by immunofluorescence and Western blot. The number and structure of synapses in transplanted regions were observed by electron microscopy. Results (1) Immunofluorescence staining showed that NSC-induced neurons highly expressed SYN and GAP-43 at the protein levels; (2) the expression of SYN and GAP-43 significantly increased in the NSC group versus the PBS group (F= 58.367, P<0.01; F= 75.296, P<0.01). No difference existed in the SYN level between NSC and WT groups (P>0.05). However, the GAP-43 expression was significantly higher than that of the WT group (P<0.01); (3) ultrastructure showed that the number of synapses in the NSC group with normal morphology (12.1±2.1) increased than that in the PBS group (6.5±2.2) (F= 15.981, P<0.01). No difference existed between NSC and WT groups (11.0±1.4) (P>0.05). Conclusion NSC-induced neurons increase the number of synapses by an up-regulation of synaptic proteins, SYN and GAP-43. Thus synaptogenesis may be a key factor in improving the symptom of AD mice.
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