[1]张海英,刘亦恒,付媛,等.海马内注射PrPC抗体对APPswe/PSEN1dE9转基因小鼠学习和记忆的影响[J].南方医科大学学报,2018,(04):443.
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海马内注射PrPC抗体对APPswe/PSEN1dE9转基因小鼠学习和记忆的影响()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2018年04期
页码:
443
栏目:
出版日期:
2018-04-30

文章信息/Info

Title:
Effect of intrahippocampal injection of anti-cellular prion protein monoclonal antibody on cognitive deficits in APPswe/PSEN1dE9 transgenic mice
作者:
张海英刘亦恒付媛陈鹏程陆睿李剑星陈明会杨浩池张雨生
关键词:
细胞型朊蛋白阿尔茨海默病APPswe/PSEN1dE9转基因小鼠
Keywords:
cellular prion protein Alzheimer’s disease APPswe/PSEN1dE9 transgenic mice
摘要:
目的观察海马内注射PrPC 抗体后,对APPswe/PSEN1dE9 转基因小鼠认知缺陷的影响。方法选8 月龄雄APPswe/ PSEN1dE9转基因小鼠双侧海马内注射PrPC抗体EP1802Y 2 μL或PBS 2 μL,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/PSEN1dE9 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PrPC抗体可以部分 改善APPswe/PSEN1dE9转基因小鼠的认知能力,提示海马内封闭PrPC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。
Abstract:
Objective To study the effects of intrahippocampal injection of cellular prion protein (PrPC) antibody on cognitive deficits of APPswe/PSEN1dE9 transgenic mice. Methods Eight-month-old male APPswe/PSEN1dE9 transgenic mice were subjected to bilateral intrahippocampal injection of a single dose (2 μL) of anti-PrPC monoclonal antibody (EP1802Y) or PBS, with wild-type C57Bl/6J 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 EP1802Ytreated 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 EP1802Y-treated and PBS-treated mice showed significantly reduced crossings of the hidden platform as compared with the wild-type mice (P<0.05), but EP1802Y-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 EP1802Y-treated mice. Conclusion Intrahippocampal injection of PrPC antibody can improve cognitive deficits of APPswe/PSEN1dE9 transgenic mice, which sheds light on a novel therapeutic approach for Alzheimer’s disease that targets PrPC to lower the toxicity of Aβ oligomer.

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更新日期/Last Update: 1900-01-01