解放军医学杂志2018，Vol.43Issue(4)：271-277,7.DOI:10.11855/j.issn.0577-7402.2018.04.01
CYP46A1过表达对阿尔茨海默病转基因模型小鼠的认知改善和抗炎症作用
Overexpression of CYP46A1 has anti-Alzheimer's disease like effects
摘要
Abstract
Objective To investigate the effect of CYP46A1 on the pathogenesis of Alzheimer's disease.Methods Recombinant lentiviral vectors which including anthropogenic CYP46A1 were injected into bilateral hippocampus of 3-monthold male 5XFAD transgenic mice,while empty vectors were injected into the corresponding position of the control group.After two months,the ability of learning and memory were tested by Morris water maze and T maze experiments,and amyloid plaque and inflammatory infiltration in the brain were detected by immunohistochemical staining and ELISA respectively.Results Compared with the control group,CYP46A1 virus injection significantly increased the CYP46A1 mRNA and protein expression in hippocampus.In addition,CYP46A1 overexpression significantly decreased the latency to find the platform in Morris water maze test and increased the correct rate to choose in T maze test.Aβ immunohistochemical staining and plaques area statistics demonstrated that the amyloid plaque area of hippocampus in CYP46A1 overexpression mice was significantly reduced,and there was a significantly decrease of hippocampal astrocytes expression by means of GFAP staining.Furthermore,hippocampal CYP46A1 overexpression significantly decreased the expression level of Aβ40,Aβ42,IL-1β and TNF-α,while compare with the control group.Conclusion CYP46A1 overexpression in hippocampus can promote the cognitive impairment,as well as ameliorate the brain inflammatory infiltration in 5XFAD transgenic mice,suggesting that CYP46A1 has anti-Alzheimer's disease like effects.关键词
阿尔茨海默病/CYP46A1/5XFAD转基因小鼠/学习记忆/炎症Key words
Alzheimer's disease/CYP46A1/5XFAD transgenic mice/learning and memory/inflammation分类
医药卫生引用本文复制引用
赵敏,孔彦莹,严华成,刘乐斌,苏建新,周志坚,于德宪,彭秋菊,谢丽..CYP46A1过表达对阿尔茨海默病转基因模型小鼠的认知改善和抗炎症作用[J].解放军医学杂志,2018,43(4):271-277,7.基金项目
国家自然科学基金(81100945) （81100945）
广州市珠江科技新星专项(2013J2200027).This work was supported by the National Natural Science Foundation of China (81100945) and the Pearl River Science and Technology Nova of Guangzhou (2013J2200027) （2013J2200027）
