5-Aza-CdR通过Notch1通路对小鼠海马神经发生的影响  

Effects of 5-Aza-CdR on hippocampal neurogenesis in mice via the Notch1 pathway

作　　者：王报捷 苏丽晴 张志勇[2] 闫磊 王志广 包素雅 邵国 WANG Baojie;SU Liqing;ZHANG Zhiyong;YAN Lei;WANG Zhiguang;BAO Suya;SHAO Guo(Department of Pharmacy,the Third People’s Hospital of Longgang District,Shenzhen 518112;China.2.Key Laboratory of Hypoxia Translational Medicine,Baotou Medical College,Baotou 014040;.3.Chongqing Medical University,Chongqing 400016;.4.Center for Translational Medicine,the Third People’s Hospital of Longgang District,Shenzhen 518112)

机构地区：[1]深圳市龙岗区第三人民医院药学部,深圳518112 [2]包头医学院低氧转化医学重点实验室,内蒙古包头014040 [3]重庆医科大学,重庆400016 [4]深圳市龙岗区第三人民医院转化医学中心,深圳518112

出　　处：《中国比较医学杂志》2024年第1期34-39,共6页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金(82060337);深圳市科技计划项目基础研究面上项目(JCYJ20220531092412028,JCYJ20230807121306012);深圳市龙岗区医疗卫生科技计划项目(LGKCYLWS2021000033,LGKCYLWS2023025)。

摘　　要：目的研究5-Aza-CdR对Notch1通路影响及神经再生的影响,并通过小鼠主动回避行为实验来探讨5-Aza-CdR对小鼠学习记忆能力的影响。方法将60只6~8周龄SPF级ICR雄性小鼠分为两组,通过侧脑室注射(i.c.v)给一组小鼠注射5-Aza-CdR,另一组注射BSA作为对照组。注射后24 h通过Real-time PCR和Western blot检测Notch1和HES1的mRNA和蛋白表达水平;通过激光共聚焦显微镜观察5-溴-2’-脱氧尿苷(BrdU)阳性细胞和海马DG中Notch1的表达;用MS-PCR检测Notch1甲基化变化;通过穿梭回避实验来评估小鼠的学习和记忆行为。结果注射5-Aza-CdR使海马Notch1通路活性增加并促进DG区神经细胞再生,降低Notch1启动子区甲基化水平,小鼠主动回避行为能力得到提升。结论5-Aza-CdR对小鼠主动回避行为的影响可能与Notch1通路影响海马神经再生有关。Objective To investigate the effect of 5-Aza-CdR on Notch1 pathway and neural regeneration and to explore the effects of 5-Aza-CdR on learning memory ability in mice by exploring active avoidance behavior.Methods Sixty 6~8-week-old SPF-grade ICR male mice were divided into two groups.5-Aza-CdR was administered to one group of mice via lateral ventricular injection,while the control group was injected with bovine serum albumin.Notch1 and HES1 mRNA and protein expression levels were detected by Real-time PCR and Western blot 24 hours after injection;5-bromo2’-deoxyuridine-positive cells were observed by laser confocal microscopy,and Notch1 expression in hippocampal dentate gyrus was viewed with laser confocal microscopy.Notch1 methylation changes were detected by ethylation-specific PCR,and learning and memory behaviors of mice were assessed by passive avoidance tests and shuttle avoidance assays.Results Injection of 5-Aza-CdR increased hippocampal Notch1 pathway activity,promoted neuronal regeneration in the DG region,decreased methylation levels in the Notch1 promoter region,and enhanced the ability of mice to perform active avoidance behavior.Conclusions The effect of 5-Aza-CdR on active avoidance behavior may be related to the influence of hippocampal neural regeneration through the Notch1 pathway.

关 键 词：5-AZA-CDR 神经发生 NOTCH1 学习和记忆 

分 类 号：R-33[医药卫生]