Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Localized in vivo 13C NMR spectroscopy of the brain.

ABSTRACT: Localized (13)C NMR spectroscopy provides a new investigative tool for studying cerebral metabolism. The application of (13)C NMR spectroscopy to living intact humans and animals presents the investigator with a number of unique challenges. This review provides in the first part a tutorial insight into the ingredients required for achieving a successful implementation of localized (13)C NMR spectroscopy. The difficulties in establishing (13)C NMR are the need for decoupling of the one-bond (13)C-(1)H heteronuclear J coupling, the large chemical shift range, the low sensitivity and the need for localization of the signals. The methodological consequences of these technical problems are discussed, particularly with respect to (a) RF front-end considerations, (b) localization methods, (c) the low sensitivity, and (d) quantification methods. Lastly, some achievements of in vivo localized (13)C NMR spectroscopy of the brain are reviewed, such as: (a) the measurement of brain glutamine synthesis and the feasibility of quantifying glutamatergic action in the brain; (b) the demonstration of significant anaplerotic fluxes in the brain; (c) the demonstration of a highly regulated malate-aspartate shuttle in brain energy metabolism and isotope flux; (d) quantification of neuronal and glial energy metabolism; and (e) brain glycogen metabolism in hypoglycemia in rats and humans. We conclude that the unique and novel insights provided by (13)C NMR spectroscopy have opened many new research areas that are likely to improve the understanding of brain carbohydrate metabolism in health and disease.

SUBMITTER: Gruetter R

PROVIDER: S-EPMC1513184 | biostudies-other | 2003 Oct-Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Assessment of metabolic fluxes in the mouse brain in vivo using 1H-[13C] NMR spectroscopy at 14.1 Tesla.

Project description:(13)C magnetic resonance spectroscopy (MRS) combined with the administration of (13)C labeled substrates uniquely allows to measure metabolic fluxes in vivo in the brain of humans and rats. The extension to mouse models may provide exclusive prospect for the investigation of models of human diseases. In the present study, the short-echo-time (TE) full-sensitivity (1)H-[(13)C] MRS sequence combined with high magnetic field (14.1 T) and infusion of [U-(13)C6] glucose was used to enhance the experimental sensitivity in vivo in the mouse brain and the (13)C turnover curves of glutamate C4, glutamine C4, glutamate+glutamine C3, aspartate C2, lactate C3, alanine C3, γ-aminobutyric acid C2, C3 and C4 were obtained. A one-compartment model was used to fit (13)C turnover curves and resulted in values of metabolic fluxes including the tricarboxylic acid (TCA) cycle flux VTCA (1.05 ± 0.04 μmol/g per minute), the exchange flux between 2-oxoglutarate and glutamate Vx (0.48 ± 0.02 μmol/g per minute), the glutamate-glutamine exchange rate V(gln) (0.20 ± 0.02 μmol/g per minute), the pyruvate dilution factor K(dil) (0.82 ± 0.01), and the ratio for the lactate conversion rate and the alanine conversion rate V(Lac)/V(Ala) (10 ± 2). This study opens the prospect of studying transgenic mouse models of brain pathologies.

| S-EPMC4420852 | biostudies-literature

Determination of oxidative glucose metabolism in vivo in the young rat brain using localized direct-detected ¹³C NMR spectroscopy.

Project description:Determination of oxidative metabolism in the brain using in vivo ¹³C NMR spectroscopy (¹³C MRS) typically requires repeated blood sampling throughout the study to measure blood glucose concentration and fractional enrichment (input function). However, drawing blood from small animals, such as young rats, placed deep inside the magnet is technically difficult due to their small total blood volume. In the present study, a custom-built animal holder enabled temporary removal of the animal from the magnet for blood collection, followed by accurate repositioning in the exact presampling position without degradation of B? shimming. ¹³C label incorporation into glutamate C4 and C3 positions during a 120 min [1,6-¹³C?] glucose infusion was determined in 28-day-old rats (n = 4) under ?-chloralose sedation using localized, direct-detected in vivo ¹³C MRS at 9.4T. The tricarboxylic acid cycle activity rate (V(TCA)) determined using a one-compartment metabolic modeling was 0.67 ± 0.13 ?mol/g/min, a value comparable to previous ex vivo studies. This methodology opens the avenue for in vivo measurements of brain metabolic rates using ¹³C MRS in small animals.

| S-EPMC3184325 | biostudies-literature

Kinetic analysis of glycogen turnover: relevance to human brain 13C-NMR spectroscopy.

Project description:A biophysical model of the glycogen molecule is developed, which takes into account the points of attack of synthase and phosphorylase at the level of the individual glucose chain. Under the sole assumption of steric effects governing enzyme accessibility to glucosyl residues, the model reproduces the known equilibrium structure of cellular glycogen at steady state. In particular, experimental data are reproduced assuming that synthase (1) operates preferentially on inner chains of the molecule and (2) exhibits a faster mobility than phosphorylase in translocating from an attacked chain to another. The model is then used to examine the turnover of outer versus inner tiers during the labeling process of isotopic enrichment (IE) experiments. Simulated data are fitted to in vivo (13)C nuclear magnetic resonance spectroscopy measurements obtained in the human brain under resting conditions. Within this experimental set-up, analysis of simulated label incorporation and retention shows that 7% to 35% of labeled glucose is lost from the rapidly turning-over surface of the glycogen molecule when stimulation onset is delayed by 7 to 11.5 hours after the end of [1-(13)C]glucose infusion as done in actual procedures. The substantial label washout before stimulation suggests that much of the subsequent activation-induced glycogenolysis could remain undetected. Overall, these results show that the molecular structure significantly affects the patterns of synthesis and degradation of glycogen, which is relevant for appropriate design of labeling experiments aiming at investigating the functional roles of this glucose reserve.

| S-EPMC3790939 | biostudies-other

State of the art direct 13C and indirect 1H-[13C] NMR spectroscopy in vivo. A practical guide.

Project description:Carbon-13 NMR spectroscopy in combination with (13)C-labeled substrate infusion is a powerful technique for measuring a large number of metabolic fluxes noninvasively in vivo. It has been used to quantify glycogen synthesis rates, establish quantitative relationships between energy metabolism and neurotransmission, and evaluate the importance of different substrates. Measurements can, in principle, be performed through direct (13)C NMR detection or via indirect (1)H-[(13)C] NMR detection of the protons attached to (13)C nuclei. The choice of detection scheme and pulse sequence depends on the magnetic field strength, whereas substrate selection depends on metabolic pathways. (13)C NMR spectroscopy remains a challenging technique that requires several nonstandard hardware modifications, infusion of (13)C-labeled substrates, and sophisticated processing and metabolic modeling. In this study, the various aspects of direct (13)C and indirect (1)H-[(13)C] NMR are reviewed with the aim of providing a practical guide.

| S-EPMC3694136 | biostudies-other

13C INEPT diffusion-ordered NMR spectroscopy (DOSY) with internal references.

Project description:13C INEPT Diffusion-ordered NMR spectroscopy (DOSY) with an internal reference system was developed to study the aggregation state of THF-solvated LDA dimeric complex. Six components are clearly identified in the diffusion dimension, and their DOSY-generated 13C INEPT spectrum slices agree extremely well with their respective INEPT spectra. The correlation between log D and log FW of the linear least-squares fit to reference points of all components is exceptionally high: (r = 0.9985).

| S-EPMC3220947 | biostudies-literature

Dynamic nuclear polarization-enhanced 13C NMR spectroscopy of static biological solids.

Project description:We explore the possibility of using dynamic nuclear polarization (DNP) to enhance signals in structural studies of biological solids by solid state NMR without sample spinning. Specifically, we use 2D (13)C-(13)C exchange spectroscopy to probe the peptide backbone torsion angles (φ, ψ) in a series of selectively (13)C-labeled 40-residue β-amyloid (Aβ(1-40)) samples, in both fibrillar and non-fibrillar states. Experiments are carried out at 9.39 T and 8 K, using a static double-resonance NMR probe and low-power microwave irradiation at 264 GHz. In frozen solutions of Aβ(1-40) fibrils doped with DOTOPA-TEMPO, we observe DNP signal enhancement factors of 16-21. We show that the orientation- and frequency-dependent spin polarization exchange between sequential backbone carbonyl (13)C labels can be simulated accurately using a simple expression for the exchange rate, after experimentally determined homogeneous (13)C lineshapes are incorporated in the simulations. The experimental 2D (13)C-(13)C exchange spectra place constraints on the φ and ψ angles between the two carbonyl labels. Although the data are not sufficient to determine φ and ψ uniquely, the data do provide non-trivial constraints that could be included in structure calculations. With DNP at low temperatures, 2D (13)C-(13)C exchange spectra can be obtained from a 3.5 mg sample of Aβ(1-40) fibrils in 4 h or less, despite the broad (13)C chemical shift anisotropy line shapes that are observed in static samples.

| S-EPMC3660528 | biostudies-literature

Protein backbone dynamics through 13C'-13Calpha cross-relaxation in NMR spectroscopy.

Project description:Internal dynamics of proteins are usually characterized by the analysis of (15)N relaxation rates that reflect the motions of NH(N) vectors. It was suggested a decade ago that additional information on backbone motions can be obtained by measuring cross-relaxation rates associated with intra-residue C'C(alpha) vectors. Here we propose a new approach to such measurements, based on the observation of the transfer between two-spin orders 2N(z)() and 2N(z)(). This amounts to "anchoring" the and operators to the N(z)() term from the amide of the next residue. In combination with symmetrical reconversion, this method greatly reduces various artifacts. The experiment is carried out on human ubiquitin at 284.1 K, where the correlation time is 7.1 ns. The motions of the C'C(alpha) vector appear more restricted than those of the NH(N) vector.

| S-EPMC2365922 | biostudies-literature

Long-range correlations between aliphatic 13C nuclei in protein MAS NMR spectroscopy.

Project description: Not available

| S-EPMC2982996 | biostudies-literature

Evaluation of cerebral acetate transport and metabolic rates in the rat brain in vivo using 1H-[13C]-NMR.

Project description:Acetate is a well-known astrocyte-specific substrate that has been used extensively to probe astrocytic function in vitro and in vivo. Analysis of amino acid turnover curves from (13)C-acetate has been limited mainly for estimation of first-order rate constants from exponential fitting or calculation of relative rates from steady-state (13)C enrichments. In this study, we used (1)H-[(13)C]-Nuclear Magnetic Resonance spectroscopy with intravenous infusion of [2-(13)C]acetate-Na(+) in vivo to measure the cerebral kinetics of acetate transport and utilization in anesthetized rats. Kinetics were assessed using a two-compartment (neuron/astrocyte) analysis of the (13)C turnover curves of glutamate-C4 and glutamine-C4 from [2-(13)C]acetate-Na(+), brain acetate levels, and the dependence of steady-state glutamine-C4 enrichment on blood acetate levels. The steady-state enrichment of glutamine-C4 increased with blood acetate concentration until 90% of plateau for plasma acetate of 4 to 5 mmol/L. Analysis assuming reversible, symmetric Michaelis-Menten kinetics for transport yielded 27+/-2 mmol/L and 1.3+/-0.3 micromol/g/min for K(t) and T(max), respectively, and for utilization, 0.17+/-0.24 mmol/L and 0.14+/-0.02 micromol/g/min for K(M_util) and V(max_util), respectively. The distribution space for acetate was only 0.32+/-0.12 mL/g, indicative of a large excluded volume. The astrocytic and neuronal tricarboxylic acid cycle fluxes were 0.37+/-0.03 micromol/g/min and 1.41+/-0.11 micromol/g/min, respectively; astrocytes thus comprised approximately 21%+/-3% of total oxidative metabolism.

| S-EPMC2879471 | biostudies-literature

Localized 1H NMR spectroscopy in different regions of human brain in vivo at 7 T: T2 relaxation times and concentrations of cerebral metabolites.

Project description:At the high field strength of 7 T, in vivo spectra of the human brain with exceptional spectral quality sufficient to quantify 16 metabolites have been obtained previously only in the occipital lobe. However, neurochemical abnormalities associated with many brain disorders are expected to occur in brain structures other than the occipital lobe. The purpose of the present study was to obtain high-quality spectra from various brain regions at 7 T and to quantify the concentrations of different metabolites. To obtain concentrations of metabolites within four different regions of the brain, such as the occipital lobe, motor cortex, basal ganglia and cerebellum, the T(2) relaxation times of the singlets and J-coupled metabolites in these regions were measured for the first time at 7 T. Our results demonstrate that high-quality, quantifiable spectra can be obtained in regions other than the occipital lobe at 7 T utilizing a 16-channel transceiver coil and B(1)(+) shimming.

| S-EPMC3357544 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data