产前酒精暴露抑制了发育大脑中自和突触蛋白的暂时表达
Monica Hampe1, Nune Darbinian1, Nana Merabova1,2
1Center for Neural Development and Repair, Department of Neural Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
概括
产前酒精暴露会通过抑制自和突触连接来损害胎儿大脑发育. 外体体中miR-9的减少可能预测胎儿酒精谱系障碍 (FASD).
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
- 毒理学 毒理学 毒理学
背景情况:
- 胎儿酒精谱系障碍 (FASD) 涉及神经元亡和自抑制,影响突触连接.
- 对人类胎儿大脑中自机制的研究是有限的.
- 产前酒精暴露 (EtOH) 与胎儿大脑衍生外体 (FB-Es) 中的miRNA-9水平降低有关,与FAS特征相关.
研究的目的:
- 在产前EtOH暴露的背景下,研究自和突触可塑性的分子机制.
- 探索miRNA-9在EtOH诱导的神经发育变化的作用.
- 为了确定FASD预测的潜在生物标志物.
主要方法:
- 使用了一种以EtOH液体饮食和人类胎儿大脑组织 (9-23周GA) 的老鼠模型.
- 通过问卷评估EtOH的消耗.
- 分析了84个突触可塑性基因,miRNA-9和脑组织和FB-E中的蛋白质的表达,使用微阵列,qRT-PCR,滴滴数字PCR,qWestern blot和ELISA.
主要成果:
- 在胎儿大脑中,EtOH暴露增加了亲亡的标记物,并抑制了胎儿大脑中的抗亡和自亡相关基因 (例如,Bag3).
- 突触蛋白 (synaptophysin,synapsin) 和参与长期潜能/抑郁症的基因被下调;TNFα被上调.
- 在FB-Es中观察到减少的miR-9标和突触基因表达,反映了大脑组织的发现.
结论:
- 产前暴露于EtOH会破坏大鼠和人类胎儿大脑的自和突触可塑性.
- 这涉及GSK3β/β-catenin信号的失调.
- 减少的miR-9目标突触基因在FB-Es中显示出作为预测FASD的新生物标志物具有前途.
关键词:
酒精饮料 酒精饮料 酒精饮料 酒精饮料细胞灭亡 (apoptosis) 是一种死亡的过程.自自是一种自的过程.外基因组是外基因组的组成部分.这就是 FASD 的原因.胎儿大脑 胎儿大脑突触性可塑性 突触性可塑性更多相关视频
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