In vivo quantification of neuro-glial metabolism and glial glutamate concentration using 1H-[13C] MRS at 14.1T
Article first published online: 11 NOV 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 128, Issue 1, pages 125–139, January 2014
How to Cite
J. Neurochem. (2014) 128, 125–139.
- Issue published online: 17 DEC 2013
- Article first published online: 11 NOV 2013
- Accepted manuscript online: 4 OCT 2013 01:28AM EST
- Manuscript Accepted: 19 SEP 2013
- Manuscript Revised: 31 AUG 2013
- Manuscript Received: 5 MAR 2013
- Swiss National Science Foundation. Grant Number: 131087
- Centre d'Imagerie BioMédicale (CIBM) of the UNIL, UNIGE, HUG, CHUV, EPFL, and the Leenaards and Jeantet Foundations
- 13C MRS;
- acetate metabolism;
- glial TCA cycle;
- glutamate/glutamine cycle;
- metabolic modeling;
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 13C NMR spectroscopy coupled with the infusion labeled glial-specific substrate, such as acetate. In this study, we infused alpha-chloralose anesthetized rats with [2-13C]acetate and followed the dynamics of the fractional enrichment (FE) in the positions C4 and C3 of glutamate and glutamine with high sensitivity, using 1H-[13C] 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 (Vg) of 0.27 ± 0.02 μmol/g/min and a glutamatergic neurotransmission rate (VNT) 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 (VPC) was 0.09 ± 0.01 μmol/g/min, corresponding to 37% of the glial glutamine synthesis rate. The glial and neuronal transmitochondrial fluxes (Vxg and Vxn) 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 13C-acetate labeling study, we propose a refined two-compartment analysis of brain energy metabolism based on 13C 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.