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

  • Basic Neurosciences, Genetics and Immunology - Original Article
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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.

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Acknowledgments

The authors are grateful to Mr. Christopher Johnson, Drs. Steve Li, Steve Fox and Su Xu for valuable help and Ms. Ioline Henter for editing the manuscript. This work was supported by the Intramural Research Program of the NIH, NIMH.

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Authors and Affiliations

  1. Molecular Imaging Branch, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Health Bldg. 10, Rm. 2D51A, 9000 Rockville Pike, Bethesda, MD, 20892-1527, USA

    Jehoon Yang & Jun Shen

  2. Samsung Biomedical Research Institute, 50 Ilwon-dong, Kangnam-Gu, Seoul, Korea

    Jehoon Yang

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  1. Jehoon Yang
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  2. Jun Shen
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Correspondence to Jun Shen.

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Yang, J., Shen, J. Elevated endogenous GABA concentration attenuates glutamate–glutamine cycling between neurons and astroglia. J Neural Transm 116, 291–300 (2009). https://doi.org/10.1007/s00702-009-0186-0

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  • DOI: https://doi.org/10.1007/s00702-009-0186-0

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