Gene expression of glucose transporters and glycolytic enzymes in the CNS of rats behaviorally dependent on ethanol.
The steady-state levels of messenger RNA (mRNA) of the glucose transporters 1 and 3 and the glycolytic enzymes hexokinase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase and pyruvate dehydrogenase were measured in up to seven brain regions of the rat in a recently developed animal model of 'behavioral dependence' on ethanol. Irreversible behavioral dependence, including loss of control, was induced by offering the rats the choice between ethanol and water over a 9-month period (Group A). This group was compared with a group given the choice between ethanol and water for only 2 months (not yet behaviorally dependent, Group B), a group forced to consume ethanol as sole fluid over a 9-month period (not behaviorally dependent, Group C) and ethanol-naive control rats. All groups were sacrificed 1 month after ethanol withdrawal. The mRNA concentrations of both neuronal glucose transporter 3 and the key glycolytic enzymes phosphofructokinase and pyruvate dehydrogenase were significantly reduced in the hippocampi of the rats behaviorally dependent on ethanol (Group A). No significant changes were seen in any of the remaining brain regions (e.g., cortical areas, limbic forebrain, amygdala, midbrain) in Group A, or in any brain area at all in Groups B and C. The results show that chronic consumption of ethanol in a free-choice situation may impair neuronal glucose uptake and glycolytic flux. This effect is manifested exclusively in the hippocampus and is specifically related to the development of behavioral dependence, since it was not found after forced administration of large amounts of ethanol (Group C).
Department of Radiological Diagnostics and Nuclear Medicine, Klinikum Benjamin Franklin, Free University of Berlin, D-12200, Berlin, Germany.
M
M
Eravci
S
S
Kley
G
G
Pinna
H
H
Prengel
O
O
Brödel
L
L
Hiedra
H
H
Meinhold
A
A
Baumgartner
D000437:Alcoholism / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D015342:DNA Probes; D000431:Ethanol / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006593:Hexokinase / Q000235:genetics; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000737:chemistry / Q000201:enzymology*; D010732:Phosphofructokinase-1 / Q000235:genetics; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D015342:DNA Probes; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D011768:Pyruvate Dehydrogenase Complex; D012333:RNA, Messenger; C495690:Slc2a3 protein, rat; D000431:Ethanol; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D006593:Hexokinase; D010732:Phosphofructokinase-1; D005947:Glucose