内皮-Ercc1 DNA 修复缺陷导致血脑屏障功能障碍
Cathrin E Hansen1,2,3, Davide Vacondio4,5, Lennart van der Molen4,6
1Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. c.e.hansen@amsterdamumc.nl.
Cell death & disease
|January 3, 2025
概括
由DNA损伤修复缺陷 (ERCC1缺乏) 驱动的脑内皮细胞衰老会损害血脑屏障的完整性,并促进神经炎症. 这种细胞衰老有助于认知能力下降和大脑平衡的破坏.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 遗传学 遗传学 是一个
背景情况:
- 大脑血管的衰老与神经血管和神经退行性疾病有关.
- 人们对内皮细胞 (EC) 基因组不稳定性在大脑平衡中的作用知之甚少.
- DNA 损伤显著加速细胞衰老.
研究的目的:
- 研究内皮老化如何影响血脑屏障 (BBB) 功能.
- 检查大脑EC中DNA修复缺陷对BBB完整性和大脑平衡的影响.
主要方法:
- 在实验室中利用了ERCC1缺乏的人类大脑ECs.
- 采用了EC特定的Ercc1淘汰 (EC-KO) 鼠标模型.
- 评估了BBB完整性,衰老标志物,血管生成途径和免疫细胞透.
主要成果:
- 缺乏ERCC1的ECs表现出衰老,减少BBB完整性,并通过Dll4-Notch通路失调增加发芽.
- 在EC-KO小鼠中,P21+细胞,血管生成标记物,EC和细胞周细胞的增加.
- EC-KO小鼠显示了BBB泄漏,免疫细胞透到白质中,并增强了粘附分子表达.
结论:
- 内皮老化,与ERCC1缺乏相关,驱动BBB功能障碍.
- 内皮老化促进了芽和免疫细胞向大脑迁移.
- 这些与衰老相关的变化有助于大脑平衡的受损.
更多相关视频
06:19Author Spotlight: A Personalized Approach Towards Investigating Alzheimer's Disease Using an In Vitro Blood-Brain Barrier Model
Published on: October 20, 2023
1.8K
10:50Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo
Published on: March 26, 2019
7.6K
相关概念视频
00:49The Blood-brain Barrier
46.2K
Overview
46.2K
01:38Nucleotide Excision Repair
3.4K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.4K