In vivo quantification of neuro-glial metabolism and glial glutamate concentration using H-1-[C-13] MRS at 14.1T

摘要

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 C-13 NMR spectroscopy coupled with the infusion labeled glial-specific substrate, such as acetate. In this study, we infused alpha-chloralose anesthetized rats with [2-C-13] acetate and followed the dynamics of the fractional enrichment (FE) in the positions C4 and C3 of glutamate and glutamine with high sensitivity, using H-1-[C-13] 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 mu mol/g/min and a glutamatergic neurotransmission rate (V-NT) of 0.15 +/- 0.01 mu mol/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 mu mol/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 mu mol/g. The effect of spectral data quality on the fluxes estimates was analyzed by Monte Carlo simulations.