5-Aza-CdR通过Notch1通路对小鼠海马神经发生的影响
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1.深圳市龙岗区第三人民医院药学部;2.包头医学院;3.重庆医科大学;4.深圳市龙岗区第三人民医院转化医学中心

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国家自然科学基金项目(面上项目,重点项目,重大项目)


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

1.Shenzhen Longgang District Third People‘s Hospital;2.Shenzhen Longgang District Third People's Hospital;3.Baotou Medical College;4.包头医学院

Fund Project:

The National Natural Science Foundation of China (General Program, Key Program, Major Research Plan)

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    摘要:

    【摘要】 目的:研究5-Aza-CdR对Notch1通路影响及神经再生的影响,并通过探讨对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的作用。方法:将60只6~8周龄ICR雄性SPF级小鼠分为两组,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小时通过实时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了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;通过测量被动回避测试和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通过Notch1通路影响海马神经再生有关。

    Abstract:

    【 Abstract】 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 behavioral experiments on mice. Methods Sixty 6- to 8-week-old ICR male SPF-grade mice were divided into two groups, and 5-Aza-CdR was administered to one group of mice via lateral ventricular injection (i.c.v.), while the other group was injected with BSA as a control group. 5-Aza-CdR was administered to mice by lateral ventricular injection (i.c.v). mRNA and protein expression levels of Notch1 and HES1 were detected by real-time PCR and Western blot 24 hours after injection; 5-bromo-2'-deoxyuridine (BrdU)-positive cells were observed by laser confocal microscopy and Notch1 expression in hippocampal DG by laser confocal microscopy; Notch1 methylation changes were detected by MS-PCR; and learning and memory behaviours of mice were assessed by measuring passive avoidance tests and shuttle avoidance assays. RESULTS Injection of 5-Aza-CdR increased hippocampal Notch1 pathway activity and 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 behaviour. Conclusion The effect of 5-Aza-CdR on active avoidance behavior may be related to the influence of hippocampal neural regeneration through the Notch1 pathway.

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  • 收稿日期:2023-04-14
  • 最后修改日期:2023-09-13
  • 录用日期:2024-01-05
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