Elevated endogenous GABA concentration attenuates glutamate-glutamine cycling between neurons and astroglia.
In this study, the relationship between endogenous brain GABA concentration and glutamate-glutamine cycling flux (V (cyc)) was investigated using in vivo (1)H and (1)H{(13)C} magnetic resonance spectroscopy techniques. Graded elevations of brain GABA levels were induced in rat brain after administration of the highly specific GABA-transaminase inhibitor vigabatrin (gamma-vinyl-GABA). The glial-specific substrate [2-(13)C]acetate and (1)H{(13)C} magnetic resonance spectroscopy were used to measure V (cyc) at different GABA levels. Significantly reduced V (cyc) was found in rats pretreated with vigabatrin. The reduction in group mean V (cyc) over the range of GABA concentrations investigated in this study (1.0 +/- 0.3-5.1 +/- 0.5 micromol/g) was found to be nonlinear: Delta V (cyc)/V (cyc) = [GABA (micromol/g)](-0.35 )- 1.0 (r (2) = 0.98). The results demonstrate that V (cyc) is modulated by endogenous GABA levels, and that glutamatergic and GABAergic interactions can be studied in vivo using noninvasive magnetic resonance spectroscopy techniques.
Yang
Jehoon
J
Molecular Imaging Branch, National Institute of Mental Health Intramural Research Program, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-1527, USA.
Shen
Jun
J
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000085:Acetates / Q000008:administration & dosage / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002247:Carbon Isotopes / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D007275:Injections, Intravenous; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020888:Vigabatrin / Q000008:administration & dosage / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000085:Acetates; D002247:Carbon Isotopes; D002250:Carbon Radioisotopes; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin