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瓦尔酸对胎儿大脑转录组的快速作用:对大脑发育和自闭症的影响

Susan G Dorsey¹, Evelina Mocci^1,2, Malcolm V Lane³

¹Department of Pain and Translational Symptom Science University of Maryland School of Nursing, Baltimore, MD, 21201, USA.

Translational psychiatry

|December 5, 2024

概括

产前接触抗药物酸 (VPA) 会改变胎儿小鼠大脑中的基因表达,可能影响神经发育并增加自闭症风险. 这项研究确定了因VPA暴露而失调的关键基因.

科学领域:

神经科学是一个神经科学.
遗传学是一个遗传学.
发育生物学发展生物学

背景情况:

酸 (VPA) 是一种抗和情绪稳定药物.
产前VPA暴露与自闭症发病率的增加有关,并在动物模型中引起自闭症类症状.
在发育中的胎儿大脑中,VPA迅速影响基因表达.

研究的目的:

在胎儿大脑中识别被VPA显著改变的小鼠基因.
寻找与自闭症相关的基因或对胚胎神经发育至关重要的基因.
了解VPA对调节大脑连接性的基因的影响.

主要方法:

在母体VPA给药后,从E12.5胎儿小鼠大脑中分析RNA-seq数据.
基因表达变化的量化 (上调和下调).
将受VPA影响的基因与已知的自闭症风险基因和神经发育基因进行比较.

主要成果:

在胎儿小鼠大脑中,VPA显著改变了大约7300个基因的表达.
在VPA诱导的基因表达中没有发现任何显著的性别差异.
399个自闭症风险基因和258个其他神经发育基因的表达被VPA显著改变.

结论:

VPA对参与关键神经发育过程的基因进行失调,包括神经发生,信号通路和突触功能.
已识别的VPA失调基因为了解自闭症的潜在机制提供了潜在的目标.
这项研究强调了VPA对胎儿大脑基因表达和神经发育的深刻影响.

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