The focus of this proposal is the cerebral metabolism of acetate derived from ethanol. Acetate is the breakdown product of hepatic ethanol metabolism, and acetate is a substrate for cerebral metabolism in astrocytes. Astrocytes are responsible for removing the excitatory neurotransmitter glutamate from the extracellular space. We hypothesize that metabolic adaptation by astrocytes to use acetate as a substrate may hamper the ability of these cells to clear extracellular glutamate when acetate becomes unavailable during ethanol withdrawal. The initial aim of this proposal will determine the extent to which cerebral metabolism of acetate occurs following ethanol consumption. We will administer Carbon-13 enriched ethanol and analyze trafficking of this tracer into cerebral amino acids by Carbon-13 NMR spectroscopy of serum and extracts of brain and liver. Using similar techniques, we will determine whether cerebral utilization of acetate increases following chronic ethanol exposure.
The second aim will determine whether chronic ethanol exposure alters cerebral metabolism of acetate and glucose during withdrawal from ethanol in a manner that could contribute to withdrawal-induced hyperexcitability. ? ? ?
