Ceramide metabolism analysis in a model of binge drinking reveals both neuroprotective and toxic effects of ethanol.
J Neurochem
; 131(5): 645-54, 2014 Dec.
Article
en En
| MEDLINE
| ID: mdl-25060779
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 C160, C180, and C200 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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Depresores del Sistema Nervioso Central
/
Ceramidas
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Etanol
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Consumo Excesivo de Bebidas Alcohólicas
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
J Neurochem
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos