Detection of reduced GABA synthesis following inhibition of GABA transaminase using in vivo magnetic resonance signal of [13C]GABA C1.
Previous in vivo magnetic resonance spectroscopy (MRS) studies of gamma-aminobutyric acid (GABA) synthesis have relied on (13)C label incorporation into GABA C2 from [1-(13)C] or [1,6-(13)C(2)]glucose. In this study, the [(13)C]GABA C1 signal at 182.3 ppm in the carboxylic/amide spectral region of localized in vivo (13)C spectra was detected. GABA-transaminase of rat brain was inhibited by administration of gabaculine after pre-labeling of GABA C1 and its metabolic precursors with exogenous [2,5-(13)C(2)]glucose. A subsequent isotope chase experiment was performed by infusing unlabeled glucose, which revealed a markedly slow change in the labeling of GABA C1 accompanying the blockade of the GABA shunt. This slow labeling of GABA at elevated GABA concentration was attributed to the relatively small intercompartmental GABA-glutamine cycling flux that constitutes the main route of (13)C label loss during the isotope chase. Because this study showed that using low RF power broadband stochastic proton decoupling is feasible at very high field strength, it has important implications for the development of carboxylic/amide (13)C MRS methods to study brain metabolism and neurotransmission in human subjects at high magnetic fields.
Yang
Jehoon
J
National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.
Johnson
Christopher
C
Shen
Jun
J
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000818:Animals; D001923:Brain Chemistry; D002247:Carbon Isotopes; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004574:Electromagnetic Fields; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation*; D051381:Rats; D012815:Signal Processing, Computer-Assisted; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis*
D002247:Carbon Isotopes; D003509:Cyclohexanecarboxylic Acids; D004791:Enzyme Inhibitors; C012987:gabaculine; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase