Metabolic Interplay between Astrocytes and Neurons Regulates Endocannabinoid Action. Cell Rep 2015 Aug 04;12(5):798-808
Date
07/28/2015Pubmed ID
26212325Pubmed Central ID
PMC4526356DOI
10.1016/j.celrep.2015.06.075Scopus ID
2-s2.0-84938548918 (requires institutional sign-in at Scopus site) 95 CitationsAbstract
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.
Author List
Viader A, Blankman JL, Zhong P, Liu X, Schlosburg JE, Joslyn CM, Liu QS, Tomarchio AJ, Lichtman AH, Selley DE, Sim-Selley LJ, Cravatt BFAuthor
Qing-song Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsArachidonic Acids
Astrocytes
Cell Communication
Endocannabinoids
Glycerides
Mice
Mice, Knockout
Monoacylglycerol Lipases
Neurons
Receptor, Cannabinoid, CB1
