Quantification of cortical GABA-glutamine cycling rate using in vivo magnetic resonance signal of [2-13C]GABA derived from glia-specific substrate [2-13C]acetate.
Brain [2-(13)C]gamma-aminobutyric acid (GABA) signal derived from the glia-specific substrate [2-(13)C]acetate reflects the extent of the GABA-glutamine neurotransmitter cycling between GABAergic neurons and glial cells. We report, for the first time, in vivo quantification of the GABA-glutamine cycling flux. The GABA-glutamine cycling flux rate was determined to be 1.8+/-0.4 micromol/(gh) (mean+/-S.D., n=6, approximately 6% of total tricarboxylic acid cycle rate) in the neocortex of vigabatrin-treated rats. The relatively small magnitude of glial contribution to the clearance of extracellular GABA measured in this study provided in vivo evidence to support the concept of a significant neuronal reuptake of GABA, which short-circuits the GABA-glutamine cycling pathway for repletion of released neurotransmitter GABA.
Yang
Jehoon
J
National Institute of Mental Health Intramural Research Program, 9000 Rockville Pike, Bethesda, MD, USA.
Li
Shizhe S
SS
Bacher
John
J
Shen
Jun
J
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D007700:Kinetics; D008253:Macaca mulatta; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009457:Neuroglia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020888:Vigabatrin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000085:Acetates; D003509:Cyclohexanecarboxylic Acids; D004791:Enzyme Inhibitors; D005973:Glutamine; C012987:gabaculine; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin; D005947:Glucose