Quantification of cortical GABA-glutamine cycling rate using in vivo magnetic resonance signal of [2-C-13]GABA derived from glia-specific substrate [2-C-13]acetate

Brain [2-C-13] gamma-aminobutyric acid (GABA) signal derived from the glia-specific substrate [2-C-13]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 mu mol/(g h) (mean +/- S.D., n = 6, similar to 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. (c) 2006 Elsevier Ltd. All rights reserved.