Drebrin和SYP在APP/PS1转基因AD小鼠海马内的表达与认知障碍的关系  

Relationship between the expressions of drebrin and SYP in hippocampus with cognitive decline in an APP/PS1 transgenic model of AD mouse

作　　者：柴继侠[1,2] 姚君茹[1] 于剑锋[1] 陈明军[1] 徐冲冲[1] 朱新平[1] 陈祖林 李瑞锡[1] 彭裕文[1] 

机构地区：[1]复旦大学上海医学院解剖与组织胚胎学系,上海200032 [2]蚌埠医学院组织胚胎学教研室,蚌埠233030 [3]洛克菲勒大学神经生物学和遗传学实验室,纽约10021

出　　处：《神经解剖学杂志》2009年第3期273-278,共6页Chinese Journal of Neuroanatomy

摘　　要：已知Alzheimer病(AD)患者脑内的主要病理变化之一是树突棘与突触的退化,而树突棘与突触的正常发育及病理改变均与树突棘肌动蛋白结合蛋白drebrin和突触前成分内突触素(synaptophysin,SYP)的表达水平密切相关。为探讨drebrin和SYP的表达与AD认知障碍之间的关系,本实验先采用Morris水迷宫法观测了6、9、12月龄APP/PS1转基因小鼠和同种野生型小鼠的学习记忆能力;再用Western blot法检测了其海马内drebrin和SYP蛋白表达水平。结果显示:9月龄APP/PS1转基因小鼠海马内drebrin蛋白的表达水平已有下降,其学习记忆能力也相应地降低,12月龄时二者下降明显;但作为突触前成分中的SYP蛋白表达水平的下降则较前二者的出现为迟。本结果提示,drebrin的表达下降在AD早期行为学改变的分子机制中发挥重要的作用,而SYP的表达下降则在drebrin下降之后参与AD的进一步发展。It has been well known that the degeneration of the dendritic spine and synapse is one of the major pathological changes in the brains with Alzheimer disease （AD）, which is closely related with the expression levels of the drebrin, an actin binding protein, and the synaptophysin （SYP） located in the presynaptic element. In order to understand the relationship between the expressions of the drebrin and SYP with the cognitive decline in AD, the present study examined the expressions of tbe drebrin and SYP in hippocampus by means of tbe Western blot in the APP/PS1 transgenic mouse aged 6, 9 and 12 months after the animals were tested for the ability in learning and memory by a Morris water maze. The results revealed that the expression level of the drebrin in hippocampus was decreased and the ability in learning and memory was accordingly decreased in the APP/PS1 transgenie mouse aged 9 months, and the decreases both in expression of the drebrin and in learning and memory were more obvious in the mouse aged 12 months. However, the expression level of the SYP descen- ded much later compared with the decreases of the drebrin and the animal cognition. These results indicate that the decrease of the drebrin might play an important role in the molecular mechanisms underlining the decline in cognition at the early stages of AD, while the decrease of the expression in SYP, which follows the expression change of the drebrin, might participate in the further development of AD.

关 键 词：肌动蛋白结合蛋白 突触素 Alzheimer病 水迷宫 APP/PS1转基因小鼠 

分 类 号：R749.16[医药卫生—神经病学与精神病学]