Year: 2015
Type: article
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.
Source: Cell Reports
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: G120164892, G1738202334, G1885050812, Regulation of dopamine neuronal activity and depressive behavior by HCN channels, Lipidomic mapping of the cellular anatomy of brain endocannabinoid metabolism, G3593117897, G3593534703, G3841156357, Monoacylglycerol Lipase Inhibitors for Treating Opioid Use Disorders, G485770986, G524874629, G5542784096, G738808116, G7978545332, Mechanistic studies of cAMP effectors in cocaine addiction, G862412000
OpenAlex ID: W1494787392