衰老对天体细胞对大脑内皮细胞信号传递的影响
Shuzhen Guo1, Gen Hamanaka1, Fang Zhang1
1Neuroprotection Research Laboratory, Departments of Radiology and Neurology Massachusetts General Hospital and Harvard Medical School Charlestown MA USA.
概括
星球细胞中的细胞衰老通过增加血管素原 (AGT) 信号传递,损害了血脑屏障 (BBB). 降低老年星球细胞中的AGT恢复了BBB功能,这表明对老年中枢神经系统疾病的治疗点.
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
- 衰老研究研究 衰老研究
背景情况:
- 衰老显著影响中枢神经系统 (CNS) 功能,包括血脑屏障 (BBB) 的完整性.
- 细胞衰老,衰老的标志,正在通过星球细胞-大脑内皮细胞相互作用对改变BBB功能的潜在作用进行研究.
研究的目的:
- 为了确定星细胞衰老是否影响BBB属性.
- 调查血管素信号传递在调解与天体细胞衰老相关的BBB变化的作用.
主要方法:
- 人类天体细胞和大脑微血管内皮细胞在低通道和高通道培养,以诱导衰老.
- 通过β-galactosidase染色和CDKN2A基因表达来确认衰老.
- 共同培养被用来评估大脑内皮细胞的透性,使用Alexa Fluor 488标记的BSA追踪器.
- 在衰老的星球细胞中使用siRNA调节 angiotensinogen (AGT) 表达.
主要成果:
- 年轻的天体细胞增强了BBB基因表达,降低了内皮透性.
- 衰老的星体细胞失去了促进BBB完整性的能力 (122.8%±28.6%对比45.5%±18.0%).
- 在衰老的星体细胞中,AGT水平升高,通过siRNA减少AGT恢复了老年星体细胞的BBB促进作用.
结论:
- 星球细胞增加的血管激素信号,有助于降低衰老中枢神经系统中的BBB功能.
- 向星性血管激素信号可能提供一个策略,以减轻与年龄相关的BBB功能障碍.
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