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- Title
Ceramide metabolism analysis in a model of binge drinking reveals both neuroprotective and toxic effects of ethanol.
- Authors
Bae, Mihyun; Bandaru, Veera Venkata Ratnam; Patel, Neha; Haughey, Norman J.
- 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.
- Subjects
BINGE drinking; CERAMIDES; ETHANOL; NEUROPROTECTIVE agents; LABORATORY mice; ALCOHOLIC intoxication; THERAPEUTICS
- Publication
Journal of Neurochemistry, 2014, Vol 131, Issue 5, p645
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.12834