首页|5-Aza-CdR通过Notch1通路对小鼠海马神经发生的影响

5-Aza-CdR通过Notch1通路对小鼠海马神经发生的影响

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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。
Effects of 5-Aza-CdR on hippocampal neurogenesis in mice via the Notch1 pathway
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-bromo-2'-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 Notch 1 pathway.

5-Aza-CdRneurogenesisNotch 1learning and memory

王报捷、苏丽晴、张志勇、闫磊、王志广、包素雅、邵国

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深圳市龙岗区第三人民医院药学部,深圳 518112

包头医学院低氧转化医学重点实验室,内蒙古包头 014040

重庆医科大学,重庆 400016

深圳市龙岗区第三人民医院转化医学中心,深圳 518112

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5-Aza-CdR 神经发生 Notch1 学习和记忆

国家自然科学基金深圳市科技计划项目基础研究面上项目深圳市科技计划项目基础研究面上项目深圳市龙岗区医疗卫生科技计划项目深圳市龙岗区医疗卫生科技计划项目

82060337JCYJ20220531092412028JCYJ20230807121306012LGKCYLWS2021000033LGKCYLWS2023025

2024

中国比较医学杂志
中国实验动物学会,中国医学科学院医学实验动物研究所

中国比较医学杂志

CSTPCD北大核心
影响因子:0.473
ISSN:1671-7856
年,卷(期):2024.34(1)
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