title: Ceramide metabolism analysis in a model of binge drinking reveals both neuroprotective and toxic effects of ethanol.
abstract: Binge drinking is a common form of alcohol abuse that involves repeated rounds of intoxication followed by withdrawal. The episodic effects of binge drinking and withdrawal on brain resident cells are thought to contribute to neural remodeling and neurological damage. However, the molecular mechanisms for these neurodegenerative effects are not understood. Ethanol (EtOH) regulates the metabolism of ceramide, a highly bioactive lipid that is enriched in brain. We used a mouse model of binge drinking to determine the effects of EtOH intoxication and withdrawal on brain ceramide metabolism. Intoxication and acute alcohol withdrawal were each associated with distinct changes in ceramide regulatory genes and metabolic products. EtOH intoxication was accompanied by decreased concentrations of multiple ceramides, coincident with reductions in the expression of enzymes involved in the production of ceramides, and increased expression of ceramide-degrading enzymes. EtOH withdrawal was associated with specific increases in ceramide C16:0, C18:0, and C20:0 and increased expression of enzymes involved with ceramide production. These data suggest that EtOH intoxication may evoke a ceramide phenotype that is neuroprotective, whereas EtOH withdrawal results in a metabolic shift that increases the production of potentially toxic ceramide species.
authors: Richard T. Johnson Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Mihyun
authors: M
authors: Bae
authors: Veera Venkata Ratnam
authors: VV
authors: Bandaru
authors: Neha
authors: N
authors: Patel
authors: Norman J
authors: NJ
authors: Haughey
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D063425:Binge Drinking / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000008:administration & dosage* / Q000633:toxicity*; D002518:Ceramides / Q000378:metabolism*; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage* / Q000633:toxicity*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D013109:Sphingomyelins / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000517:prevention & control
chemical_list: D002492:Central Nervous System Depressants; D002518:Ceramides; D013109:Sphingomyelins; D000431:Ethanol
keywords: alcohol; binge drinking; brain; ceramide; ethanol