Endocannabinoids regulate the activity of astrocytic hemichannels and the microglial response against an injury: In vivo studies. Neurobiol Dis 2015 Jul;79:41-50
Date
04/29/2015Pubmed ID
25917763DOI
10.1016/j.nbd.2015.04.005Scopus ID
2-s2.0-84928599358 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
Anandamide (AEA) is an endocannabinoid (EC) that modulates multiple functions in the CNS and that is released in areas of injury, exerting putative neuroprotective actions. In the present study, we have used intravital microscopy to analyze the role of the EC system in the glial response against an acute insult. Our data show that AEA modulates astroglial function in vivo by increasing connexin-43 hemichannel (HC) activity. Furthermore, the genetic inactivation of the AEA-degrading enzyme, fatty acid amide hydrolase (FAAH), also increased HC activity and enhanced the microglial response against an acute injury to the brain parenchyma, effects that were mediated by cannabinoid CB1 receptors. The contribution of ATP released through an astrocytic HC was critical for the microglial response, as this was prevented by the use of the HC blocker flufenamic acid and by apyrase. As could be expected, brain concentrations of AEA, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were elevated in FAAH-null mice, while 2-arachidonoylglycerol (2-AG) concentrations remained unaltered. In summary, these findings demonstrate that AEA modifies glial functions by promoting an enhanced pro-inflammatory glial response in the brain.
Author List
Vázquez C, Tolón RM, Pazos MR, Moreno M, Koester EC, Cravatt BF, Hillard CJ, Romero JAuthor
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAmides
Amidohydrolases
Animals
Anti-Inflammatory Agents
Apyrase
Arachidonic Acids
Astrocytes
Brain
Brain Injuries
Connexin 43
Disease Models, Animal
Endocannabinoids
Ethanolamines
Flufenamic Acid
Glycerides
Lasers
Mice
Mice, Knockout
Mice, Transgenic
Microglia
Oleic Acids
Palmitic Acids
Polyunsaturated Alkamides
Receptor, Cannabinoid, CB1
