Metabolic Interplay between Astrocytes and Neurons Regulates Endocannabinoid Action
| Autor: | Dana E. Selley, Aaron J. Tomarchio, Jacqueline L. Blankman, Xiaojie Liu, Peng Zhong, Joel E. Schlosburg, Christopher M. Joslyn, Benjamin F. Cravatt, Andreu Viader, Laura J. Sim-Selley, Aron H. Lichtman, Qing-song Liu |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Nervous system
Cell signaling Cannabinoid receptor Arachidonic Acids Cell Communication Biology General Biochemistry Genetics and Molecular Biology Article Glycerides Mice Receptor Cannabinoid CB1 medicine Animals lcsh:QH301-705.5 Neuroinflammation Mice Knockout Neurons Endocannabinoid system Monoacylglycerol Lipases Monoacylglycerol lipase Crosstalk (biology) medicine.anatomical_structure Biochemistry lcsh:Biology (General) Astrocytes Synaptic plasticity lipids (amino acids peptides and proteins) Neuroscience Endocannabinoids |
| Zdroj: | Cell Reports, Vol 12, Iss 5, Pp 798-808 (2015) |
| ISSN: | 2211-1247 |
| Popis: | SummaryThe 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. |
| Databáze: | OpenAIRE |
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