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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30AA016243-02
Application #
7285595
Study Section
Special Emphasis Panel (ZAA1-HH (52))
Program Officer
Noronha, Antonio
Project Start
2006-08-01
Project End
2008-05-31
Budget Start
2007-08-01
Budget End
2008-05-31
Support Year
2
Fiscal Year
2007
Total Cost
$26,870
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Pharmacology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599