title: Postnatal ethanol exposure alters levels of 2-arachidonylglycerol-metabolizing enzymes and pharmacological inhibition of monoacylglycerol lipase does not cause neurodegeneration in neonatal mice.
abstract: The consumption of ethanol by pregnant women may cause neurological abnormalities, affecting learning and memory processes in children, and are collectively described as fetal alcohol spectrum disorders. However, the molecular mechanisms underlying these changes are still poorly understood. In our previous studies, we found that ethanol treatment of postnatal day 7 (P7) mice significantly enhances the anandamide levels but not the 2-arachidonylglycerol (2-AG) levels and induces widespread neurodegeneration, but the reason for the lack of significant effects of ethanol on the 2-AG level is unknown. In this study, we examined developmental changes in diacylglycerol lipase-α, β (DAGL-α and β) and monoacylglycerol lipase (MAGL). We found that the levels of these proteins were significantly higher in adult brains compared to those detected early in brain development. Next, we examined the influence of P7 ethanol treatment on these enzymes, finding that it differentially altered the DAGL-α protein and mRNA levels but consistently enhanced those of the DAGL-β. Interestingly, the ethanol treatment enhanced MAGL protein and mRNA levels. Inhibition of MAGL with KML29 failed to induce neurodegeneration in P7 mice. Collectively, these findings suggest that ethanol significantly activates DAGL-β and MAGL in the neonatal brain, resulting in no net change in 2-AG levels.
authors: Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, USA.
authors: Shivakumar
authors: S
authors: Subbanna
authors: Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas, USA.
authors: Delphine
authors: D
authors: Psychoyos
authors: Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, USA.
authors: Shan
authors: S
authors: Xie
authors: Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, USA.|New York State Psychiatric Institute, College of Physicians & Surgeons, Columbia University, New York, New York, USA.|Department of Psychiatry, College of Physicians & Surgeons, Columbia University, New York, New York, USA.
authors: Balapal S
authors: BS
authors: Basavarajappa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002853:Chromatography, Liquid; D063388:Endocannabinoids / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity*; D005989:Glycerides / Q000378:metabolism*; D015151:Immunoblotting; D008071:Lipoprotein Lipase / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008994:Monoacylglycerol Lipases / Q000378:metabolism; D009410:Nerve Degeneration / Q000473:pathology*; D053284:Polyunsaturated Alkamides; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001095:Arachidonic Acids; D002492:Central Nervous System Depressants; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D000431:Ethanol; C094503:glyceryl 2-arachidonate; D008994:Monoacylglycerol Lipases; D008071:Lipoprotein Lipase; C078814:anandamide
keywords: CB1R; DAGL-α/β; anandamide; cannabinoids; development; fetal alcohol spectrum disorder