在小鼠状屏障中调节叶酸运输
Vishal Sangha1, Sara Aboulhassane1, Reina Bendayan2
1Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
Fluids and barriers of the CNS
|August 27, 2024
概括
这项研究表明,状屏障 (AB) 表达叶酸载体RFC和PCFT,而RFC表达在叶酸缺乏和PQQ治疗下增加,这表明叶酸运输到脑脊液 (CSF) 的新途径.
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
- 生物化学 生物化学
背景情况:
- 叶酸 (维生素B9) 对中枢神经系统 (CNS) 的发育至关重要.
- 主要的叶酸载体包括叶酸受体α (FRα),质子合叶酸载体 (PCFT) 和减少叶酸载体 (RFC).
- 叶酸进入大脑的运输发生在胸膜 (CP) 和血脑屏障 (BBB) 中,但对状屏障 (AB) 的作用不太了解.
研究的目的:
- 为了研究叶酸载体 (RFC,PCFT) 在AB细胞中的定位和功能.
- 通过NRF-1/PGC-1α信号传递和叶酸缺乏来研究这些载体的调节.
- 探索AB对叶酸运输到脑脊液 (CSF) 的贡献.
主要方法:
- 免疫细胞化学测定RFC和PCFT在老鼠AB细胞中的定位.
- 运输测试以评估RFC和PCFT的功能.
- 调查pyrroloquinoline quinone (PQQ) 对RFC表达的影响.
- 分析叶酸缺乏的AB细胞中的基因表达变化.
主要成果:
- 发现RFC在AB表皮上部位化,而PCFT显示基底侧和细胞内部位化.
- 通过NRF-1/PGC-1α信号传递,PQQ治疗显著增强了RFC功能表达.
- 叶酸缺乏会增加AB细胞中RFC,MRP3,P-gp,GLUT1和Claudin-5的表达.
结论:
- 在AB表现RFC和PCFT的极化表达.
- RFC功能表达是由NRF-1/PGC-1α激活和叶酸缺乏引起的.
- 该AB代表了叶酸流入CSF的潜在途径,补充了CP运输.
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