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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 Sciences, University of Maryland School of Nursing, Baltimore, MD 21201.

Research square

|January 23, 2024

概括

产前暴露于药物酸 (VPA),改变胎儿大脑中的基因表达,可能导致自闭症的发展. 这项研究确定了在发育中的小鼠大脑中由VPA暴露调节的特定基因.

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
遗传学遗传学是一个

背景情况:

产前暴露于酸 (VPA) 与自闭症谱系障碍 (ASD) 的发病率增加有关.
在子宫内,VPA暴露会在动物模型中诱导类似自闭症的行为,这表明它对神经发育有直接影响.

研究的目的:

在胎儿大脑中识别被VPA显著改变的小鼠基因.
研究VPA对自闭症风险基因和神经发育基因的影响.
为了找到理解神经发育障碍的潜在目标.

主要方法:

在VPA注射后对E12.5胎儿小鼠大脑进行RNA测序 (RNA-seq) 分析.
基因表达变化的量化 (上下调节).
分析的重点是自闭症风险基因和对胎儿大脑发育至关重要的基因.

主要成果:

在胎儿小鼠大脑中,VPA迅速改变了大约7300个基因的表达.
在VPA诱导的基因表达中没有观察到任何显著的性别差异.
399个自闭症风险基因和255个关键神经发育基因的表达受到VPA的显著影响.

结论:

暴露于VPA显著影响正常胎儿大脑发育和连接所必需的广泛基因.
已确定的VPA调节基因为了解VPA诱导的神经发育变化和ASD背后的分子机制提供了潜在的目标.

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