AD转基因模型Tg2576鼠阳性子鼠的病理和认知行为变化  

THE CHANGE OF PATHOLOGY AND COGNITIVE BEHAVIOR OF THE FIRST-GENERATION MICE OF THE TRANSGENIC MODEL OF ALZHEIMER’S DISEASE-Tg2576 MOUSE

作　　者：李国营[1] 汪华侨[1] 胡金家[2] 徐杰[1] 姚志彬[1] 

机构地区：[1]中山大学基础医学院人体解剖学教研室脑研究室 [2]上海第二医科大学人体解剖学教研室,上海200025

出　　处：《神经解剖学杂志》2006年第4期384-388,共5页Chinese Journal of Neuroanatomy

基　　金：国家重点基础研究发展计划(973计划;2006cb500700);国家自然科学基金(Nos.30400512;30470904);粤港关键领域重点突破项目(20054982210);广东省自然科学基金重大项目(No.20013137);广东省自然科学基金博士启动基金(No.5300294);广东省社会发展项目(2005B10401047);广东省医学科研基金(A2005322);广州市科技计划(Nos.2005Z3-E4021;2006J1-C0101)资助项目

摘　　要：为探讨老年性痴呆(AD)转基因模型Tg2576(hAPPSWE)鼠阳性子一代鼠的病理和行为学变化,确定其是否具有亲代的性状,为AD研究提供理想的动物模型。本研究随机选取我室繁育并鉴定的子一代hAPPSWE基因阳性鼠(hAPPSWE+)和hAPPSWE基因阴性鼠(hAPPSWE-),分别在4、7、9月龄时经Y迷宫及15月龄时经水迷宫检测其行为学变化和脑内病理变化,并对皮质和海马的淀粉样斑块进行定量研究。结果显示:(1)4月龄和7月龄的子一代hAPPSWE+鼠的空间辨别学习记忆能力与hAPPSWE-鼠相比,差异无显著性(P>0.05),但9月龄时两者之间的差异有高度显著性(P<0.01);(2)在4月龄和7月龄的子一代hAPPSWE+鼠的脑组织切片上免疫组化染色未观察到淀粉样斑块,9月龄时均观察到明显的淀粉样斑块沉积,但hAP-PSWE-鼠无论在任何1个月龄均未观察到淀粉样斑块沉积;(3)定量结果显示9月龄的子一代hAPPSWE+鼠的皮层淀粉样斑块占整个皮层面积的0.21%,海马的淀粉样斑块占海马面积的0.14%,而15月龄时其淀粉样斑块的数量和面积增加明显,占整个皮层面积的4.26%,海马的淀粉样斑块占海马面积的2.51%。上述结果表明子一代hAPPSWE+鼠的行为学变化及脑内淀粉样斑块出现的时间、部位、类型与亲代一致。因此,子一代hAPPSWE+鼠和其亲代一样可用于AD研究,本实验的定量结果也为评价AD的干预治疗效果提供了参考数据。To explore the change of pathology and cognitive behavior of the first-generation mice of the transgenic model of Alzheimer＇s disease- Tg2576 mouse, identify whether they have characteristic of their parent and supply ideal animal models for studies of AD, the firstgeneration mice with hAPPSWE- positive gene （ hAPPSWE ^＋ ） and the mice with hAPPSWE- negative gene （ hAPPSWE^- ） bred and i- dentified in our laboratory were randomly selected. Their cognitive abilities were tested by Y-maze in 4, 7 and 9 months old and examined by Morris water maze in 15 months old. The pathology of brain were observed and the area of amyloid plaque in cortex and hippocampi were quantified. The present results showed that： （ 1 ） Compared with hAPPSWE- mice, the cognitive abilities of hAPPSWE ＋ mice had no significant difference in 4, 7 months old（ P 〉0.05 ）, however, they had significant difference on cognitive abilities in 9 months old hAPPSWE ＋ mice （ P 〈 0.01 ） ; （2） No amyloid plaque in brain was observed by immunohistochemical staining in brain section of all cases in 4, 7 months old; but in 9 months old, some amyloid plaque were found in the brain sections. On the other hand, no amyloid plaque was observed in all hAPPSWE - mice; （ 3 ） In 9 months old, the percentage of the area of the amyloid plaque of cortex and hippocampus occupied the whole area of cortex and hippocampus was 0.21% and 0.14%, respectively. In 15 months old hAPPSWE^＋ mice, the amyloid burden of cortex and hippocampus had increased to 4.26% and 2.51 % , respectively. These results suggest that the cognitive change and deposition of amyloid plaque appeared at the time, in position and with style was the same as that of their parent, su the first-generation mice with hAPPSWE gene as same as their parent can be used in the study of AD. In addition, the quantitive data of this experiment offered reference for trial treatment of AD.

关 键 词：ALZHEIMER病 动物模型 病理 认知行为 Tg2576鼠/hAPPSWE鼠 

分 类 号：R-332[医药卫生]