The
chronic and acute effect of ethanol administration on the metabolic
phenotype of mouse brain was studied in a C57BL/6 mouse model of ethanol
abuse using both untargeted and targeted ultra performance liquid
chromatography-tandem mass spectrometry. Two experiments based on
either chronic (8 week) exposure to ethanol of both male and female
mice or acute exposure of male mice for 11 days, plus 2 oral gavage
doses of 25% ethanol, were undertaken. Marked differences were found
in amino acids, nucleotides, nucleosides, and related metabolites
as well as a number of different lipids. Using untargeted metabolite
profiling, acute ethanol exposure found significant decreases in several
metabolites including nucleosides, fatty acids, glycerophosphocholine,
and a number of phospholipids, while chronic exposure resulted in
increases in several amino acids with notable decreases in adenosine,
acetylcarnitine, and galactosylceramides. Similarly, targeted metabolite
analysis, focusing on the hydrophilic fraction of the brain tissue
extract, identified significant decreases in the metabolism of amino
acids and derivatives, as well as purine degradation especially after
chronic exposure to ethanol.