13C NMR spectroscopy applications to brain energy metabolism

Abstract

13C nuclear magnetic resonance (NMR) spectroscopy is the method of choice for studying brain metabolism. Indeed, the most convincing data obtained to decipher metabolic exchanges between neurons and astrocytes have been obtained using this technique, thus illustrating its power. It may be difficult for non-specialists, however, to grasp thefull implication of data presented in articles written by spectroscopists. The aim of the review is, therefore, to provide a fundamental understanding of this topic to facilitate the non-specialists in their reading of this literature. In the first part of this review, we present the metabolic fate of 13C-labeled substrates in the brain in a detailed way, including an overview of some general neurochemical principles. We also address and compare the various spectroscopic strategies that can be used to study brain metabolism. Then, we provide an overview of the 13C NMR experiments performed to analyze both intracellular and intercellular metabolic fluxes. More particularly, the role of lactate as a potential energy substrate for neurons is discussed in the light of 13C NMR data. Finally, new perspectives and applications offered by 13C hyperpolarization are described.

A neuronal MCT2 knockdown in the rat somatosensory cortex reduces both the NMR lactate signal and the BOLD response during whisker stimulation

“…Estimation of the PC activity corroborates this result. Indeed, quantification of Gln C2/C3 ratio is a suitable approach to evaluate this specific astrocytic anaplerotic enzyme activity; ratio higher than one indicating 13 C-incorporation through the PC activity (this pathway leads to direct 13 C-incorporation into glutamine carbon position 2 [27]). On the contrary, since no PC activity is present in neurons, the Glu C2/C3 ratio is always lower than 1 [50].…”

“…Rats were infused with a solution containing [1- 13 C glucose] (750mM, Cambridge isotope, 99% enrichment) + lactate (sodium salt, 534mM). [1-13C]glucose will labeled different amino acids and metabolites through glycolysis and the TCA cycle [15,27]. Since one mole of [1-13C]glucose gives one mole of labeled [3-13C]pyruvate and one mole of unlabeled pyruvate, there is an isotopic dilution of 50% at the end of glycolysis.…”

A dual‐tuned13C/1H head coil forPET/MRhybrid neuroimaging: Development, attenuation correction, and first evaluation

“…The natural abundance of 13 C is low; consequently, the SNR of 13 C signal in MRI and MRS is rather low as well. 13 C hyperpolarization can provide a strong boost of the 13 C signal . Thus, the full diagnostic potential for such a dual‐tuned RF coil is provided in a setting where 13 C hyperpolarization and a PET/MR system are available.…”

“…27 Among the wealth of MR imaging (MRI) and MR spectroscopy (MRS) methods, 13 C NMR is the method of choice for studying brain and cancer metabolism. 28,29 Complementing structural proton ( 1 H) MR imaging, 13 C carbon MRS provides additional diagnostic criteria for tumor characterization and patient stratification. 29,30 The combination of integrated PET/MR with 13 C MRS and MRI potentially offers simultaneous dual-modality metabolic imaging.…”

Physiological Maintenance in Animal Experiments

“…Scanning at physiological temperature is therefore particularly important when rates of transformation of one metabolite to another are being studied, for example, in the rapidly expanding field of 13 C-hyperpolarization where the pyruvate-to-lactate flux is a key interest. 1,2 The adoption of more modern, relatively nontoxic, inhaled anesthetics has greatly improved the ability to maintain good physiological condition of animals in the scanner compared with earlier injectable agents. There is nowadays relatively robust commercial equipment available employing a range of techniques for monitoring temperature and breathing rates -the essential parameters for maintaining physiological Figure 1.…”