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孕期德克萨米他暴露会影响海马刺激性突触传递和学习和记忆功能,具有跨代影响

Mingcui Luo^1,2, Yiwen Yi^3,2, Songqiang Huang^3,2

¹Department of Obstetrics, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.

Acta pharmaceutica Sinica. B

|September 18, 2023

概括

产前德克萨米他暴露 (PDE) 通过影响海马突触传输,在几代后代的后代大鼠中损害学习和记忆. 这些效应可能与miR-133a-3p信号通路有关.

科学领域:

神经科学是一个神经科学.
发展生物学发展生物学
遗传学是一个遗传学.

背景情况:

海马神经元中的突触可塑性调节学习和记忆.
葡萄糖皮质类药物,如甲,在怀孕期间在临床上被广泛使用.
产前接触某些物质可能对后代的神经发育产生长期影响.

研究的目的:

调查产前德克萨米他暴露 (PDE) 对大鼠后代学习和记忆的持久影响.
探索PDE对突触功能的代际影响和潜在的分子机制.

主要方法:

在怀孕期间,老鼠暴露于德克萨米他.
评估后代的学习和记忆缺陷 (新奇的识别,空间学习).
河马突触传输,神经递质/受体功能以及miR-133a-3p-SIRT1-CDK5-NR2B通路在几代人之间进行了分析.

主要成果:

产前德克萨米他暴露 (PDE) 在成年后代中引起了显著的学习和记忆障碍.
这些缺陷和受损的海马刺激突触传输持续跨代,直到F3代.
改变的海马体miR-133a-3p信号被确定为一个关键机制,可能通过卵细胞传播.
周围血液中的CDK5已成为潜在的早期预警标记物.

结论:

产前暴露于德克萨米他对海马突触传输和认知功能具有多代不良影响.
该miR-133a-3p-SIRT1-CDK5-NR2B通路参与调解这些跨代效应.
CDK5可以作为胎儿起源的学习和记忆障碍的预测生物标志物.

关键词:

德克萨米他是一种早期预警标记器的标记.在海马体内,海马体基因组乙化基因组乙化学习和记忆障碍学习和记忆障碍这是一个微型RNA.突触传输是通过突触传输进行的.跨代遗传是一种跨代遗传.

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