Gabrielli Martina, Battista Natalia, Riganti Loredana, Prada Ilaria, Antonucci Flavia, Cantone Laura, Matteoli Michela, Maccarrone Mauro, Verderio Claudia
Department of Medical Biotechnology and Translational Medicine, University of Milano, Milano, Italy.
Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy European Center for Brain Research/IRCCS Santa Lucia Foundation, Rome, Italy.
EMBO Rep. 2015 Feb;16(2):213-20. doi: 10.15252/embr.201439668. Epub 2015 Jan 7.
Endocannabinoids primarily influence neuronal synaptic communication within the nervous system. To exert their function, endocannabinoids need to travel across the intercellular space. However, how hydrophobic endocannabinoids cross cell membranes and move extracellularly remains an unresolved problem. Here, we show that endocannabinoids are secreted through extracellular membrane vesicles produced by microglial cells. We demonstrate that microglial extracellular vesicles carry on their surface N-arachidonoylethanolamine (AEA), which is able to stimulate type-1 cannabinoid receptors (CB1), and inhibit presynaptic transmission, in target GABAergic neurons. This is the first demonstration of a functional role of extracellular vesicular transport of endocannabinoids.
内源性大麻素主要影响神经系统内的神经元突触通讯。为发挥其功能，内源性大麻素需要穿过细胞间空间。然而，疏水性内源性大麻素如何穿过细胞膜并在细胞外移动仍是一个未解决的问题。在此，我们表明内源性大麻素是通过小胶质细胞产生的细胞外膜泡分泌的。我们证明小胶质细胞外膜泡在其表面携带N-花生四烯酰乙醇胺（AEA），它能够刺激1型大麻素受体（CB1），并抑制靶GABA能神经元的突触前传递。这是内源性大麻素细胞外囊泡运输功能作用的首次证明。
