海马内注射PrP^C抗体对APPswe/PSEN1^(dE9)转基因小鼠学习和记忆的影响  

Effect of intrahippocampal injection of anti-cellular prion protein monoclonal antibody on cognitive deficits in APPswe/PSEN1^(dE9) transgenic mice

作　　者：张海英[1] 刘亦恒[2] 付媛[1] 陈鹏程 陆睿 李剑星 陈明会 杨浩池 张雨生[1] ZHANG Haiying;LIU Yiheng;FU Yuan;CHEN Pengcheng;LU Rui;LI Jianxing;CHEN Minghui;YANG Haochi;ZHANG Yusheng(Department of Anatomy, Hainan Medical University, Haikou 571101, China;Haikou Hospital Affiliated to Central South University Xiangya School of Medicine, Haikou 570208, China)

机构地区：[1]海南医学院人体解剖学教研室,海南海口571101 [2]中南大学湘雅医学院附属海口医院,海南海口570208

出　　处：《南方医科大学学报》2018年第4期443-449,共7页Journal of Southern Medical University

基　　金：国家自然科学基金(81660224;81100246);海南省重点研发计划项目(ZDYF2017120);国家级大学生创新创业训练计划项目(201711810010);海南省自然科学基金(818MS063)~~

摘　　要：目的观察海马内注射PrP^C抗体后,对APPswe/PSEN1^(dE9)转基因小鼠认知缺陷的影响。方法选8月龄雄APPswe/PSEN1^(dE9)转基因小鼠双侧海马内注射PrP^C抗体EP1802Y 2μL或PBS 2μL,C57Bl/6J野生型小鼠为正常对照。2月后,通过旷场实验、新物体识别实验、Morris水迷宫实验、条件性恐惧测试及免疫组化,观察APPswe/PSEN1^(dE9)转基因小鼠行为学及海马内Aβ1-42表达的变化。结果旷场实验中,假手术组与实验组相比,中央活动时间和活动总路程均无明显差异(P>0.05);新物体识别实验中,假手术组分辨指数与实验组分辨指数相比,无显著性差异(P>0.05);在Morris水迷宫实验的空间探索测试中,与正常组相比,假手术组和实验组穿越平台次数显著性减少(P<0.05)。并且假手术组与实验组游泳路程相比,具有显著性差异(P<0.05);在条件恐惧实验中,各组之间无显著性差异;免疫组化的结果显示,实验组小鼠海马内Aβ1-42表达下调。结论 PrP^C抗体可以部分改善APPswe/PSEN1^(dE9)转基因小鼠的认知能力,提示海马内封闭PrP^C蛋白与Aβ寡聚体结合的位点后,或许可以降低Aβ寡聚体毒性。Objective To study the effects of intrahippocampal injection of cellular prion protein（PrP^C） antibody on cognitive deficits of APPswe/PSEN1^（dE9） transgenic mice.Methods Eight-month-old male APPswe/PSEN1^（dE9） transgenic mice were subjected to bilateral intrahippocampal injection of a single dose（2 μL） of anti-PrP^C monoclonal antibody（EP1802 Y） or PBS,with wild-type C57 Bl/6 J mice serving as the control group.After two months,the mice were tested for cognitive behaviors using open filed（OF） test,Morris water maze（MWM） test,fear conditioning（FC） test,and novel object recognition（NOR） test,and immunohistochemistry was used to examine the changes in hippocampal expression of Aβ1-42.Results The EP1802 Ytreated and PBS-treated mice showed no significantly differences in the performance in OF test in terms of central activity time or total distance of activity（P〈0.05）,nor in NOR test in terms of novel object recognition index（P〈0.05）.In MWM test,the EP1802 Y-treated and PBS-treated mice showed significantly reduced crossings of the hidden platform as compared with the wild-type mice（P〈0.05）,but EP1802 Y-treated mice had a significantly shorter swimming distance to find the platform than PBS-treated mice（P〈0.05）.No significant differences were found in the results of FC test among the 3 groups.Immunohistochemistry revealed a significantly reduced expression of Aβ1-42 in the hippocampus of EP1802 Y-treated mice.Conclusion Intrahippocampal injection of PrP^C antibody can improve cognitive deficits of APPswe/PSEN1^（dE9） transgenic mice,which sheds light on a novel therapeutic approach for Alzheimer＇s disease that targets PrP^C to lower the toxicity of Aβoligomer.

关 键 词：细胞型朊蛋白 阿尔茨海默病 APPswe/PSEN1^dE9转基因小鼠 

分 类 号：R749.16[医药卫生—神经病学与精神病学]