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1、May200925(3)273～278神经解剖学杂志(ChineseJournalofNeuroanatomy)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1,211111柴继侠姚君茹于剑锋陈明军徐冲冲朱新平31313陈祖林李瑞锡彭裕文(12复旦大学上海医学院解剖与组织胚胎学系,上海200032;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)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
2、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Westernblot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SY
3、P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。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RelationshipbetweentheexpressionsofdrebrinandSYPinhippocampuswithcognitivedeclineinanAPP/PS1transgenicmodelofADmouse1,21111ChaiJixia,Ya
4、oJunru,YuJianfeng,ChenMingjun,XuChongchong,1311ZhuXinping,ChenZulin,LiRuixi,PengYuwen(1DepartmentofAnatomy,HistologyandEmbryology,ShanghaiMedicalCollege,FudanUniversity,Shanghai200032;2DepartmentofHistologyandEmbryology,BengbuMedicalCollege,Bengbu233030;3LaboratoryofNeu
5、robiologyandGenetics,TheRockefellerUniversity,NewYork10021)AbstractIthasbeenwellknownthatthedegenerationofthedendriticspineandsynapseisoneofthemajorpathologicalchangesinthebrainswithAlzheimerdisease(AD),whichiscloselyrelatedwiththeexpressionlevelsofthedrebrin,anactinbin
6、dingprotein,andthesynaptophysin(SYP)locatedinthepresynapticelement.InordertounderstandtherelationshipbetweentheexpressionsofthedrebrinandSYPwiththecognitivedeclineinAD,thepresentstudyexaminedtheexpressionsofthedrebrinandSYPinhippocampusbymeansoftheWesternblotintheAPP/PS
7、1transgenicmouseaged6,9and12monthsaftertheanimalsweretestedfortheabilityinlearningandmemo2rybyaMorriswatermaze.TheresultsrevealedthattheexpressionlevelofthedrebrininhippocampuswasdecreasedandtheabilityinlearningandmemorywasaccordinglydecreasedintheAPP/PS1transgenicmouse
8、aged9months,andthedecreasesbothinexpressionofthedrebrinandinlearningandmemoryweremoreobviousinthemouseaged12mo
