Department of Neurosurgery, Brigham and Woman's Hospital, Harvard Medical School, Boston, Massachusetts 02115-6195, United States.
Chemical Biology PhD Program, Harvard University, Cambridge, Massachusetts 02138, United States.
ACS Chem Biol. 2021 Jan 15;16(1):106-115. doi: 10.1021/acschembio.0c00779. Epub 2020 Dec 14.
The cell membrane of brain endothelial cells is enriched in omega-3 phospholipid species. Numerous omega-3 phospholipid species were recently proposed to be important for maintaining the low rate of transcytosis and, thus, could be important for regulating one of the mechanisms of the blood brain barrier (BBB). However, the spatial distribution of these phospholipid species within the brain was previously unknown. Here, we combined advanced mass spectrometry imaging techniques to generate a map of these phospholipids in the brain at near single cell resolution. Furthermore, we explored the effects of omega-3 dietary deprivation on both docosahexaenoic acid (DHA)-containing phospholipids and the global brain phospholipid profile. We demonstrate the unique spatial distribution of individual DHA-containing phospholipids, which may be important for the regiospecific properties of the BBB. Finally, 24 diet discriminative phospholipids were identified and showed an increase in saturated phospholipid species and ceramide containing phospholipid species under omega-3 dietary deficiency.
脑内皮细胞的细胞膜富含ω-3 磷脂种类。最近有大量的 ω-3 磷脂种类被提出对维持低胞吐作用率很重要，因此可能对调节血脑屏障（BBB）的其中一个机制很重要。然而，这些磷脂种类在脑内的空间分布此前尚不清楚。在这里，我们结合了先进的质谱成像技术，在接近单细胞分辨率的水平生成了脑内这些磷脂的图谱。此外，我们还探索了 ω-3 饮食剥夺对含二十二碳六烯酸（DHA）的磷脂和大脑内整体磷脂谱的影响。我们证明了个别含 DHA 的磷脂的独特空间分布，这可能对 BBB 的区域特异性性质很重要。最后，鉴定出 24 种饮食差异的磷脂，并且在 ω-3 饮食缺乏时显示出饱和磷脂种类和含有神经酰胺的磷脂种类增加。
