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在子宫内,乙醇暴露会诱导线粒体DNA损伤,并抑制发育中的大脑mtDNA修复

Nune Darbinian¹, Armine Darbinyan², Nana Merabova^1,3

¹Center for Neural Repair and Rehabilitation (Shriners Hospitals Pediatric Research Center), Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States.

Frontiers in neuroscience

|August 25, 2023

概括

母亲饮酒会损害胎儿大脑的线粒体DNA (mtDNA),这是胎儿酒精谱系障碍 (FASD) 的关键因素. 外体中受损的mtDNA可能预测FASD,IGF-1可能提供神经保护.

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:

线粒体功能障碍是胎儿酒精谱系障碍 (FASD) 的一种拟议机制.
乙醇 (EtOH) 暴露可以诱导线粒体DNA (mtDNA) 损伤和氧化应激.
由于有限的人类模型和非侵入性工具,研究FASD具有挑战性.

研究的目的:

用人类和老鼠模型研究线粒体功能障碍在FASD中的作用.
探索胎儿大脑衍生外体 (FB-Es) 作为FASD生物标志物的潜力.
评估胰岛素样生长因子1 (IGF-1) 对EtOH诱导的神经元损伤的影响.

主要方法:

比较暴露于EtOH的人类和大鼠胎儿大脑组织,神经元培养和FB-Es.
量化了mtDNA损伤,8-oxoguanine DNA glycosylase-1 (OGG1) mRNA,以及外体OGG1水平.
评估IGF-1对暴露在EtOH中的神经元的影响.

主要成果:

孕产妇暴露于EtOH会增加胎儿大脑组织和FBE的mtDNA损伤.
在FB-Es中受损的mtDNA与眼睛直径小相关,这是FASD的标志.
EtOH抑制了OGG1介导的mtDNA修复,而IGF-1则拯救了神经元免受损伤和亡.

结论:

在FB-Es中受损的mtDNA可以作为FASD的预测生物标志物.
IGF-1显示出缓解EtOH诱导的mtDNA损伤和神经元细胞死亡的潜力.

关键词:

8-oxoguanine DNA glycosylase-1 (OGG1) 是一种 8-oxoguanine 基因糖酶-1 (OGG1) 是一种 8-oxoguanine 基因糖酶-1 (OGG1) 是一种 8-oxoguanine 基因糖酶-1 (OGG1) 是一种 8-oxoguanine 基因糖酶-1 (OGG1) 是一种 8-oxoguanine 基因糖酶-1 (OGG1) 是一种 8-oxoguanine 基因糖酶-1 (OGG1) 是一种 8-oxoguanine 基因糖酶-1 (OGG1) 是一种这就是 FASD 的原因.在IGF-1的基础上,IGF-1 大脑发育大脑的发育大脑的发展外基因组是外基因组的组成部分.线粒体中的线粒体.导致mtDNA损伤.在mtDNA修复过程中.

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