Mannequin for on-demand 2-AG launch in extracellular microvesicles. Credit score: Proceedings of the Nationwide Academy of Sciences (2025). DOI: 10.1073/pnas.2421717122
Marijuana-like endocannabinoids produced by your personal physique—how do they journey via the mind? It seems that these fatty messenger molecules are transported in fatty vesicles. This stunning discovery contrasts with how conventional messenger molecules transfer. Dopamine and serotonin, for example, journey as free-floating molecules between nerve cells.
“This is possibly a new form of communication between nerve cells in the brain,” says chemist Mario van der Stelt.
Van der Stelt suspects that different fatty messenger molecules may transfer via the mind in the identical approach. This perception might result in new remedies.
“The body’s own ‘marijuana’ plays a role in pain and other neurological conditions. Now that we know how it moves, we can look for ways to influence its function,” he explains.
Why did it take so lengthy for scientists to uncover how one sort of endocannabinoid, 2-AG, is transported? The issue with 2-AG was that it couldn’t be tracked instantly.
“Because it is a fatty substance, you can’t simply see it under a microscope,” Van der Stelt says. Normal measurement strategies have been ineffective as a result of they destroyed the cells, making it unattainable to trace the substance over time.
The analysis is printed within the journal Proceedings of the Nationwide Academy of Sciences.
Glowing cells as the important thing
The breakthrough got here when Chinese language researchers developed a sensible sensor. This sensor makes use of cells that gentle up after they detect 2-AG from a neighboring nerve cell. For the primary time, this made it doable to watch 2-AG’s motion in actual time. This discovery laid the muse for 4 years of analysis, culminating within the new publication, which marks the ultimate piece of Verena Straub’s Ph.D. analysis.
Because of this sensor, Straub found that 2-AG is transported in vesicles. She examined this by isolating and analyzing the vesicles. She discovered that when she blocked 2-AG manufacturing, vesicles nonetheless shaped however not contained 2-AG. Conversely, when she prevented vesicle formation, the quantity of 2-AG decreased. On common, every vesicle contained about 2,000 2-AG molecules.
To verify the accuracy of their mannequin, the researchers examined their findings in mind tissue in collaboration with a US-based group. They discovered indications that the identical course of happens in intact mind tissue. Moreover, along with Coen van Hasselt’s group, they developed a mathematical mannequin that might solely clarify the noticed alerts if 2-AG was certainly transported through vesicles.
Extra info:
Verena M. Straub et al, The endocannabinoid 2-arachidonoylglycerol is launched and transported on demand through extracellular microvesicles, Proceedings of the Nationwide Academy of Sciences (2025). DOI: 10.1073/pnas.2421717122. On bioRxiv: www.biorxiv.org/content material/10.110 … 23.614520v1.full.pdf
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