微RNA作为产前压力相关自闭症的母体标记物,来自小鼠模型的证据
Taeseon Woo1, Candice King2, Nick I Ahmed3
1Interdisciplinary Neuroscience Program, University of Missouri, Columbia, MO 65211, USA.
Journal of personalized medicine
|September 28, 2023
概括
母亲的血清素载体 (SERT) 基因变异和产前压力相互作用,影响后代的社会行为和老鼠的重复行为. 母亲血液中的特定微RNA可能表明自闭症谱系障碍 (ASD) 风险.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 发展生物学 发展生物学
背景情况:
- 自闭症谱系障碍 (ASD) 的发病包括复杂的遗传和环境因素.
- 产前应激暴露是ASD的潜在风险因素,而血清素转运体 (SERT) 基因的短等位基因调解了这种关联.
- 母亲SERT基因型和产前压力之间的相互作用需要进一步研究与后代神经发育有关的问题.
研究的目的:
- 在小鼠模型中研究产前压力和母亲SERT基因型对后代行为的联合影响.
- 探索这些因素与怀孕期间母亲的微RNA (miRNA) 表达之间的关联.
- 为了确定ASD亚型的潜在生物标志物.
主要方法:
- 使用小鼠模型,怀孕的雌性被按基因型 (野生型或SERT异性淘汰) 和应激暴露 (慢性变量应激或控制) 分类.
- 后代的行为在出生后的第60天被评估,使用社会互动,焦虑和重复行为测试.
- 在胚胎第21天,对母体血液样本进行了miRNA表达特征分析.
主要成果:
- 暴露于压力的SERT异合体淘汰母亲的后代表现出明显减少的社会偏好,特别是男性.
- 这些后代还表现出增加的理行为,表明重复的行为,再次特别是在男性中.
- 三种特定的miRNAs (mmu-miR-7684-3p, mmu-miR-5622-3p, mmu-miR-6900-3p) 在暴露于压力的SERT异性淘汰基因型的母亲的血液中被差异地表达.
结论:
- 母亲SERT基因型和产前压力相互作用,影响后代的特定行为结果,这表明某些与ASD相关的表型的途径.
- 在怀孕后期不同表达的母体miRNAs可以作为潜在的生物标志物来识别ASD病原学的特定亚型.
- 这项研究强调了在理解ASD病因学方面考虑基因环境相互作用的重要性.
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