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In vivo quantification of neuro‐glial metabolism and glial glutamate concentration using 1 H‐[ 13 C] MRS at 14.1T
Author(s) -
Lanz Bernard,
Xin Lijing,
Millet Philippe,
Gruetter Rolf
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12479
Subject(s) - glutamate receptor , glutamatergic , glutamine , metabolism , neuroglia , chemistry , glutamine synthetase , in vivo , biochemistry , tricarboxylic acid , citric acid cycle , biophysics , biology , endocrinology , central nervous system , amino acid , receptor , microbiology and biotechnology
Astrocytes have recently become a major center of interest in neurochemistry with the discoveries on their major role in brain energy metabolism. An interesting way to probe this glial contribution is given by in vivo 13 C NMR spectroscopy coupled with the infusion labeled glial‐specific substrate, such as acetate. In this study, we infused alpha‐chloralose anesthetized rats with [2‐ 13 C]acetate and followed the dynamics of the fractional enrichment (FE) in the positions C4 and C3 of glutamate and glutamine with high sensitivity, using 1 H‐[ 13 C] magnetic resonance spectroscopy (MRS) at 14.1T. Applying a two‐compartment mathematical model to the measured time courses yielded a glial tricarboxylic acid ( TCA ) cycle rate ( V g ) of 0.27 ± 0.02 μmol/g/min and a glutamatergic neurotransmission rate ( V NT ) of 0.15 ± 0.01 μmol/g/min. Glial oxidative ATP metabolism thus accounts for 38% of total oxidative metabolism measured by NMR . Pyruvate carboxylase ( V PC ) was 0.09 ± 0.01 μmol/g/min, corresponding to 37% of the glial glutamine synthesis rate. The glial and neuronal transmitochondrial fluxes ( V x g and V x n ) were of the same order of magnitude as the respective TCA cycle fluxes. In addition, we estimated a glial glutamate pool size of 0.6 ± 0.1 μmol/g. The effect of spectral data quality on the fluxes estimates was analyzed by Monte Carlo simulations.In this 13 C‐acetate labeling study, we propose a refined two‐compartment analysis of brain energy metabolism based on 13 C turnover curves of acetate, glutamate and glutamine measured with state of the art in vivo dynamic MRS at high magnetic field in rats, enabling a deeper understanding of the specific role of glial cells in brain oxidative metabolism. In addition, the robustness of the metabolic fluxes determination relative to MRS data quality was carefully studied.