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Publication : Endocannabinoids regulate the activity of astrocytic hemichannels and the microglial response against an injury: In vivo studies.

First Author  Vázquez C Year  2015
Journal  Neurobiol Dis Volume  79
Pages  41-50 PubMed ID  25917763
Mgi Jnum  J:260342 Mgi Id  MGI:6140323
Doi  10.1016/j.nbd.2015.04.005 Citation  Vazquez C, et al. (2015) Endocannabinoids regulate the activity of astrocytic hemichannels and the microglial response against an injury: In vivo studies. Neurobiol Dis 79:41-50
abstractText  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.
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