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Loc Dinh Nguyen¹, Ly Huong Nguyen¹, Dat Xuan Dao¹

¹Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.

|June 9, 2025

概括

在发育中的大脑中激活转录因子6 (ATF6) 缺失导致小头症和新生儿死亡. 在大脑发育过程中,ATF6对于维持蛋白质静止和协调未展开的蛋白质反应 (UPR) 是至关重要的.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
发展生物学发展生物学

背景情况:

展开的蛋白质反应 (UPR) 在大脑发育过程中是活跃的,但其精确的功能尚未完全理解.
激活转录因子6 (ATF6),一个关键的UPR转换器,在神经发育中没有明确的作用.

研究的目的:

研究ATF6,特别是ATF6α和ATF6β在小鼠大脑发育中的作用.
阐明ATF6删除对神经元发育,大脑结构和UPR信号传递的影响.

主要方法:

产生Atf6a/Atf6b双条件淘汰 (dcKO) 的小鼠.
对dcKO大脑进行组织学和分子分析,以评估神经发生,细胞死亡,皮质分层,轴突突出,血管,质细胞和神经炎症.
分析与ER压力和UPR通路相关的基因表达特征.
用化学伴奏剂 (4-酸) 进行治疗,以评估救援效果.

主要成果:

在小鼠中,ATF6删除导致小头症和新生儿死亡率.
dcKO大脑表现出神经发生减少,亡增加,皮质层层受损和轴突引导缺陷.
在dcKO大脑中观察到显著的高血管,质异常和神经炎症.
ER压力标志物升高,分子伴侣减少,PERK和IRE1下游分子水平增加,如VEGFA.

结论:

在正常的小鼠大脑发育中,ATF6通过维持蛋白质稳定和调节UPR发挥着至关重要的作用.
失去ATF6会导致复杂的神经发育缺陷,包括血管和炎症问题.
化学护送治疗部分拯救了ATF6缺乏的小鼠,突出了ATF6在发展过程中管理ER压力的重要性.

关键词:

细胞生物学细胞生物学发育生物学是发展生物学.神经科学是一个神经科学.

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相关概念视频

Teratogenicity

Teratogenicity

The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...