2015 Jul 22. pii: S2211-1247(15)00725-1. doi: 10.1016/j.celrep.2015.06.075. [Epub ahead of print]
Viader A1, Blankman JL2, Zhong P3, Liu X3, Schlosburg JE4, Joslyn CM1, Liu QS3, Tomarchio AJ5, Lichtman AH5, Selley DE5, Sim-Selley LJ5, Cravatt BF6.
Abstract
The endocannabinoid 2-arachidonoylglycerol (2-AG) is a retrograde lipid messenger that modulates synaptic function, neurophysiology, and behavior. 2-AG signaling is terminated by enzymatic hydrolysis-a reaction that is principally performed by monoacylglycerol lipase (MAGL). MAGL is broadly expressed throughout the nervous system, and the contributions of different brain cell types to the regulation of 2-AG activity in vivo remain poorly understood. Here, we genetically dissect the cellular anatomy of MAGL-mediated 2-AG metabolism in the brain and show that neurons and astrocytes coordinately regulate 2-AG content and endocannabinoid-dependent forms of synaptic plasticity and behavior. We also find that astrocytic MAGL is mainly responsible for converting 2-AG to neuroinflammatory prostaglandins via a mechanism that may involve transcellular shuttling of lipid substrates. Astrocytic-neuronal interplay thus provides distributed oversight of 2-AG metabolism and function and, through doing so, protects the nervous system from excessive CB1 receptor activation and promotes endocannabinoid crosstalk with other lipid transmitter systems.
Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
- PMID:
26212325
[PubMed – as supplied by publisher]