, Volume 116, Issue 3, pp 291-300
Date: 30 Jan 2009

Elevated endogenous GABA concentration attenuates glutamate–glutamine cycling between neurons and astroglia

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Abstract

In this study, the relationship between endogenous brain GABA concentration and glutamate–glutamine cycling flux (V cyc) was investigated using in vivo 1H and 1H{13C} 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 (γ-vinyl-GABA). The glial-specific substrate [2-13C]acetate and 1H{13C} 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 μmol/g) was found to be nonlinear: ΔV cyc/V cyc = [GABA (μmol/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.