Document Type
Article
Original Publication Date
2015
Journal/Book/Conference Title
Cell Reports
Volume
12
Issue
5
DOI of Original Publication
10.1016/j.celrep.2015.06.075
Date of Submission
November 2015
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 activityin 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 astrocytescoordinately 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.
Rights
Copyright © 2015 The Authors. Published by Elsevier Inc.
Is Part Of
VCU Pharmacology and Toxicology Publications
Comments
Originally published at http://dx.doi.org/10.1016/j.celrep.2015.06.075