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相关概念视频

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Memory is one of the most vital higher mental functions of the brain. Memory is closely related to learning because it enables us to retain information and experiences from our past to use them in our present life. It also helps us to remember facts, events, and skills, such as riding a bike or swimming. There are two types of memory — declarative memory, which involves memorizing facts or events, and procedural memory, which enables us to remember how to do something like writing or...
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Novel Object Recognition Test for the Investigation of Learning and Memory in Mice
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通过YTHDF1促进海马依赖的学习和记忆

Hailing Shi1,2,3,4, Xuliang Zhang5,6, Yi-Lan Weng7,8

  • 1Department of Chemistry, The University of Chicago, Chicago, IL, USA.

Nature
|November 8, 2018
PubMed
概括

通过YTHDF1蛋白进行N6-甲基氨酸 (m6A) RNA修饰,促进神经元蛋白质合成,增强学习和记忆. 删除Ythdf1会损害小鼠的记忆和突触功能.

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科学领域:

  • 神经科学
  • 表观遗传学
  • 分子生物学

背景情况:

  • N6-甲基氨酸 (m6A) 是哺乳动物中普遍存在的RNA修饰,调节RNA命运和功能.
  • m6A在神经系统中大量存在,并影响神经功能.
  • m6A在体内mRNA转化中的作用,特别是在大脑中,在很大程度上是未被探索的.

研究的目的:

  • 研究m6A及其结合蛋白YTHDF1在成年小鼠海马中的mRNA转化中的作用.
  • 确定YTHDF1对学习,记忆和突触可塑性的影响.
  • 阐明m6A影响神经元蛋白质合成的机制.

主要方法:

  • 成年小鼠中Ythdf1的遗传删除和重新表达.
  • 对Ythdf1和Mettl3的急性突发性破坏.
  • 对YTHDF1和m6A位点进行全转录组映射.
  • 在海马神经元中进行新生蛋白质标记和绑定记者测试.

主要成果:

  • 在对神经元刺激的反应中,YTHDF1调解了m6A依赖的目标mRNA蛋白转化.
  • Ythdf1淘汰小鼠表现出学习和记忆缺陷,突触传输受损,以及长期增强.
  • 在海马神经元中以刺激依赖的方式增强YTHDF1的蛋白质合成.

结论:

  • 在刺激时,YTHDF1促进了m6A修饰的神经元mRNA的翻译.
  • 这种m6A-YTHDF1通路对于海马的学习和记忆过程至关重要.