Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure.
It has been reported that chronic and acute alcohol exposure decreases cerebral glucose metabolism and increases acetate oxidation. However, it remains unknown how much ethanol the living brain can oxidize directly and whether such a process would be affected by alcohol exposure. The questions have implications for reward, oxidative damage, and long-term adaptation to drinking. One group of adult male Sprague-Dawley rats was treated with ethanol vapor and the other given room air. After 3 wk the rats received i.v. [2-(13)C]ethanol and [1, 2-(13)C2]acetate for 2 h, and then the brain was fixed, removed, and divided into neocortex and subcortical tissues for measurement of (13)C isotopic labeling of glutamate and glutamine by magnetic resonance spectroscopy. Ethanol oxidation was seen to occur both in the cortex and the subcortex. In ethanol-naïve rats, cortical oxidation of ethanol occurred at rates of 0.017 ± 0.002 µmol/min/g in astroglia and 0.014 ± 0.003 µmol/min/g in neurons, and chronic alcohol exposure increased the astroglial ethanol oxidation to 0.028 ± 0.002 µmol/min/g (P = 0.001) with an insignificant effect on neuronal ethanol oxidation. Compared with published rates of overall oxidative metabolism in astroglia and neurons, ethanol provided 12.3 ± 1.4% of cortical astroglial oxidation in ethanol-naïve rats and 20.2 ± 1.5% in ethanol-treated rats. For cortical astroglia and neurons combined, the ethanol oxidation for naïve and treated rats was 3.2 ± 0.3% and 3.8 ± 0.2% of total oxidation, respectively. (13)C labeling from subcortical oxidation of ethanol was similar to that seen in cortex but was not affected by chronic ethanol exposure.
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Science, Wuhan, Hubei 430071, People's Republic of China.
Jie
J
Wang
Hongying
H
Du
Lihong
L
Jiang
Xiaoxian
X
Ma
Robin A
RA
de Graaf
Kevin L
KL
Behar
Graeme F
GF
Mason
D019973:Alcohol-Related Disorders / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol; D018698:Glutamic Acid; D005998:Glycine
13C-NMR catalase; acetaldehyde dehydrogenase; alcohol dehydrogenase; cytochrome P450