Ethanol downregulates N-acyl phosphatidylethanolamine-phospholipase D expression in BV2 microglial cells via epigenetic mechanisms.
Excessive ethanol drinking has deleterious effects on the brain. However, the effects of alcohol on microglia, the main mediator of the brain's innate immune response remain poorly understood. On the other hand, the endocannabinoid system plays a fundamental role in regulating microglial reactivity and function. Here we studied the effects of acute ethanol exposure to murine BV2 microglial cells on N-acyl phosphatidylethanolamine-phospholipase D (NAPE-PLD), a major synthesizing enzyme of anandamide and other N-acylethanolamines. We found that ethanol downregulated microglial NAPE-PLD expression by activating cAMP/PKA and ERK1/2. These signaling pathways converged on increased phosphorylation of CREB. Moreover, ethanol induced and increase in histone acetyltransferase activity which led to higher levels of acetylation of histone H3. Taken together, our results suggest that ethanol actions on microglial NAPE-PLD expression might involve epigenetic mechanisms.
Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine, University of Buenos Aires, Argentina. Electronic address: fcorrea@fmed.uba.ar.
Fernando
F
Correa
Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine, University of Buenos Aires, Argentina.
Andrea
A
De Laurentiis
Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine, University of Buenos Aires, Argentina.
Ana María
AM
Franchi
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D051548:Histone Acetyltransferases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010739:Phospholipase D / Q000235:genetics*; D013997:Time Factors
D000242:Cyclic AMP; D017362:Cyclic AMP Response Element-Binding Protein; D000431:Ethanol; D051548:Histone Acetyltransferases; D010739:Phospholipase D; C506062:Napepld protein, mouse
Endocannabinoid system; Epigenetics; Microglial activation; Neuroinflammation