10月龄APP/PS1双转基因AD小鼠海马超微结构特征的观察

Ultrostructure characteristics of hippocampus on 10 month-aged APP/PS1 transgenic AD mouse

目的:观察APP/PS1双转基因小鼠海马内Aβ沉积的形态特征。方法:以10月龄雄性APP/PS1双转基因小鼠和C57BL/6小鼠为研究对象,采用Aβ免疫组化和透射电镜技术,观察海马部位Aβ的沉积情况及相关的病理特征。结果:在双转基因小鼠海马内存在致密性神经炎性斑块及营养障碍性突起,但脑微血管壁的Aβ沉积不甚明显;营养障碍性突起及神经细胞、微血管内皮细胞、周细胞内存在大量的自噬泡及次级溶酶体,提示该模型存在自噬溶酶体途径功能紊乱。结论:该鼠模拟了AD的老年斑及相关退行性变等病理改变,其中可能伴有细胞多种代谢的变化及血脑屏障功能的变化。从老年斑角度而言,该动物是成功的阿尔茨海默病动物模型,可用于AD的生化、病理研究及新治疗方法的探索。

Objective： To observe the morphologic characteristics of Aβ deposits in hippocampus of APP/PS1 double transgenic mice. Methods： observed in 10 month-aged APP / PS1 transgenic mice and C57 BL /6 mice. By using Aβ immunochemistral staining and transmission electron microscopy,the Aβ deposit and other pathological features in hippocampus. Results： Senile deposit was seen in hippocampus of transgenic mice,mainly classic deposits composed of amyloidy core and surrounding dystrophic neurities,and diffuse deposits was also seen. Weak positive staining around some microvessels was observed. There were abundant autophagosome and late lysosome in dystrophic neurities,neurons,and endothelia and pericytes of microvessels,which present the disordered autophage / lysosome method. Conclusion： The double transgenic APP / PS1 mice mimic AD pathologic hallmark such as senile plaques and cerebral amyloid angiopathy,and some degeneration changes,accompanying changes of metabolism and function of the blood-brain barrier. The present of Aβ accumulation in the APP / PS1 model confirms its utility for studies of biochemical and pathological mechanisms underlying Aβ deposition,as well as exploring new therapeutic treatments.