中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2014年
7期
539-543
,共5页
顾国军%王培军%张炜%李铭华
顧國軍%王培軍%張煒%李銘華
고국군%왕배군%장위%리명화
阿尔茨海默病%神经干细胞%突触素%生长相关蛋白-43
阿爾茨海默病%神經榦細胞%突觸素%生長相關蛋白-43
아이자해묵병%신경간세포%돌촉소%생장상관단백-43
Alzheimer disease%Neural stem cells%Synapsins%GAP-43 protein
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.
目的 探討神經榦細胞 (NSCs) 移植對阿爾茨海默病 (AD) 小鼠突觸形成的影響.方法 9月齡20隻APP/PS1雙轉基因AD小鼠隨機分為2組,每組10隻,一組進行NSCs移植,即NSC組,另一組給予等量燐痠鹽緩遲液 (PBS) 作為陰性對照組 (PBS組),移植部位為雙側海馬區,10隻野生型小鼠作為暘性對照組 (WT組).移植8週後採用熒光免疫組化法和Western印跡檢測AD小鼠海馬區突觸素 (SYN) 和生長相關蛋白-43 (GAP-43) 錶達的變化;透射電鏡觀察移植區突觸的形態和數量.結果 (1)熒光免疫組化顯示NSCs移植分化的神經元高錶達SYN和GAP-43蛋白;(2) Western印跡顯示NSC組小鼠海馬區SYN、GAP-43錶達明顯增加,高于PBS組 (F=58.367,P<0.01;F= 75.296,P<0.01),SYN錶達與WT組小鼠相比較差異無統計學意義(P>0.05),但是NSC組小鼠GAP-43錶達高于WT組 (P<0.01);(3)超微結構顯示NSC組海馬區突觸數量增加 (12.1±2.1),多于PBS組 (6.6±1.8) (F= 15.981,P <0.01),與WT組 (11.0±1.4) 相比較差異無統計學意義 (P>0.05).結論 NSCs移植分化的神經元通過增加突觸素、GAP-43錶達來增加突觸的數量,進而建立新的突觸連接來改善AD小鼠的癥狀.
목적 탐토신경간세포 (NSCs) 이식대아이자해묵병 (AD) 소서돌촉형성적영향.방법 9월령20지APP/PS1쌍전기인AD소서수궤분위2조,매조10지,일조진행NSCs이식,즉NSC조,령일조급여등량린산염완충액 (PBS) 작위음성대조조 (PBS조),이식부위위쌍측해마구,10지야생형소서작위양성대조조 (WT조).이식8주후채용형광면역조화법화Western인적검측AD소서해마구돌촉소 (SYN) 화생장상관단백-43 (GAP-43) 표체적변화;투사전경관찰이식구돌촉적형태화수량.결과 (1)형광면역조화현시NSCs이식분화적신경원고표체SYN화GAP-43단백;(2) Western인적현시NSC조소서해마구SYN、GAP-43표체명현증가,고우PBS조 (F=58.367,P<0.01;F= 75.296,P<0.01),SYN표체여WT조소서상비교차이무통계학의의(P>0.05),단시NSC조소서GAP-43표체고우WT조 (P<0.01);(3)초미결구현시NSC조해마구돌촉수량증가 (12.1±2.1),다우PBS조 (6.6±1.8) (F= 15.981,P <0.01),여WT조 (11.0±1.4) 상비교차이무통계학의의 (P>0.05).결론 NSCs이식분화적신경원통과증가돌촉소、GAP-43표체래증가돌촉적수량,진이건립신적돌촉련접래개선AD소서적증상.
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.
