Ethanol downregulates N-acyl phosphatidylethanolamine-phospholipase D expression in BV2 microglial cells via epigenetic mechanisms

CORREA FERNANDO; CORREA FERNANDO; DE LAURENTIIS ANDREA; DE LAURENTIIS ANDREA; FRANCHI ANA MARÍA; FRANCHI ANA MARÍA

EUROPEAN JOURNAL OF PHARMACOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 786 p. 224 - 233

0014-2999

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 an 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.