Lipid transport across the blood-brain barrier

脂质转运穿过血脑屏障

• 批准号: 404540666
• 负责人: Dr. Lars Kuerschner
• 金额: --
• 依托单位: Life and Medical Sciences Institute (LIMES)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/404540666?language=en
• 关键词: Lipid; transport; across; blood; brain

In this project we aim to elucidate the selective lipid transport across the blood brain barrier (BBB) and the role of the major fascilitator superfamily domain-containing protein 2a (Mfsd2a) for this process. We want to test the hypothesis that, while initially involving Mfsd2a, the acting barrier that mediates selective lipid import into the brain in fact is a multi-stage process and includes local lipid metabolism. The project will study the individual contribution of the participating major cell types of the BBB, capillary endothelial cells and astrocytes, by characterizing their activities in lipid uptake, metabolism and trafficking. Also the role of cell-cell-connectivity for these processes will be investigated. Using the mouse model, complementary research at increasing complexity levels (in vitro and in vivo) will be conducted. The project will employ the novel alkyne lipid tracer technology that has opened a new era in lipid biology and metabolism research. These non-radioactive tracers are fully compatible with the suit of modern analytical methods and therefore allow for correlative tracking of lipid localization and metabolism at the highest spatial and analytical resolution in an unprecedented manner. We will combine alkyne lipid tracing with state-of-the-art analytics, including super-resolution microscopy and quantitative mass spectrometry (MS) lipidomics. Benefitting from this technological edge this proposal will yield important insights into the complex process of selective lipid uptake into the mammalian brain.

在这个项目中，我们的目标是阐明选择性的脂质运输通过血脑屏障（BBB）和主要fascilator超家族结构域蛋白2a（Mfsd 2a）在这一过程中的作用。我们想检验这样的假设，即虽然最初涉及Mfsd 2a，但介导选择性脂质输入大脑的作用屏障实际上是一个多阶段过程，包括局部脂质代谢。该项目将研究参与BBB的主要细胞类型，毛细血管内皮细胞和星形胶质细胞的单独贡献，通过表征它们在脂质摄取，代谢和运输中的活动。此外，这些过程中的细胞-细胞连接的作用将被调查。使用小鼠模型，将在日益复杂的水平（体外和体内）进行补充研究。该项目将采用新的炔脂质示踪技术，开辟了脂质生物学和代谢研究的新时代。这些非放射性示踪剂与现代分析方法完全兼容，因此可以以前所未有的方式以最高的空间和分析分辨率对脂质定位和代谢进行相关跟踪。我们将结合联合收割机炔脂质跟踪与最先进的分析，包括超分辨率显微镜和定量质谱（MS）脂质组学。受益于这一技术优势，这一建议将产生重要的见解选择性脂质摄取到哺乳动物大脑的复杂过程。