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Compartmentalized Cerebral Metabolism of [1,6-13C]Glucose Determined by in vivo 13C NMR Spectroscopy at 14.1 T

By João M. N. Duarte, Bernard Lanz and Rolf Gruetter


Cerebral metabolism is compartmentalized between neurons and glia. Although glial glycolysis is thought to largely sustain the energetic requirements of neurotransmission while oxidative metabolism takes place mainly in neurons, this hypothesis is matter of debate. The compartmentalization of cerebral metabolic fluxes can be determined by 13C nuclear magnetic resonance (NMR) spectroscopy upon infusion of 13C-enriched compounds, especially glucose. Rats under light α-chloralose anesthesia were infused with [1,6-13C]glucose and 13C enrichment in the brain metabolites was measured by 13C NMR spectroscopy with high sensitivity and spectral resolution at 14.1 T. This allowed determining 13C enrichment curves of amino acid carbons with high reproducibility and to reliably estimate cerebral metabolic fluxes (mean error of 8%). We further found that TCA cycle intermediates are not required for flux determination in mathematical models of brain metabolism. Neuronal tricarboxylic acid cycle rate (VTCA) and neurotransmission rate (VNT) were 0.45 ± 0.01 and 0.11 ± 0.01 μmol/g/min, respectively. Glial VTCA was found to be 38 ± 3% of total cerebral oxidative metabolism, accounting for more than half of neuronal oxidative metabolism. Furthermore, glial anaplerotic pyruvate carboxylation rate (VPC) was 0.069 ± 0.004 μmol/g/min, i.e., 25 ± 1% of the glial TCA cycle rate. These results support a role of glial cells as active partners of neurons during synaptic transmission beyond glycolytic metabolism

Topics: Neuroscience
Publisher: Frontiers Research Foundation
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Provided by: PubMed Central

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  1. (2003). 1H-localized broadband 13C NMR spectroscopy of the rat brain in vivo at 9.4
  2. (2010). 1H[13C] NMR spectroscopy of the rat brain during infusion of [2-13C] acetate at 14.1
  3. (2001). A mathematical model of compartmentalized neurotransmitter metabolism in the human brain.
  4. (2009). Acetate transport and utilization in the rat brain.
  5. (2007). Alanine metabolism, transport, and cycling in the brain.
  6. (1990). as detected by in vivo andinvitro13CNMR.J.Biol.Chem.
  7. Bamford,P.,Shi,D.,Hopkins,I.,and McKenna,M.C.(2010).Metabolism of acetyl-L-carnitine for energy and neurotransmitter synthesis in the immature rat brain.
  8. (2007). Brain pyruvate recycling and peripheral metabolism: an NMR analysis ex vivo of acetate and glucose metabolism in the rat.
  9. (2009). Caffeine consumption attenuates neurochemical modifications in the hippocampus of streptozotocininduced diabetic rats.
  10. (2003). Cerebral metabolism and consciousness.
  11. (2011). Cerebral metabolism by 13CM
  12. (2011). Cerebral metabolism by 13CM R
  13. (1993). Cerebral metabolism of [1,2-13C2]glucose and [U-13C4]3-hydroxybutyrate in rat brain as detected by 13C NMR spectroscopy.
  14. (1990). Cerebral metabolism of acetate and glucose studied by 13C-n.m.r. spectroscopy–atechniqueforinvestigating metabolic compartmentation in the brain.
  15. (2011). Compartmentalized cerebral metabolism of [1,6-13C]glucose determined by in vivo
  16. (2002). Decreased TCA cycle rate in the rat brain after acute 3-NP treatment measured by in vivo 1H-13C NMR spectroscopy.
  17. (2002). Demonstration of pyruvate recycling in primary cultures of neocortical astrocytes but not in neurons.
  18. (2003). Detection of [1,6-13C2]-glucose metabolism in rat brain by in vivo 1H-[13C]-NMR spectroscopy.
  19. (2009). Determination of the glutamate-glutamine cyclingfluxusingtwo-compartment dynamic metabolic modeling is sensitive to astroglial dilution.
  20. (2002). Development of 17O NMR approach for fast imaging of cerebral metabolic rate of oxygen in rat brain at high field.
  21. (1992). Effect of alphachloralose, halothane, pentobarbital and nitrous oxide anesthesia on metabolic coupling in somatosensory cortex of rat.
  22. (2002). Effect of deep pentobarbital anesthesia on neurotransmitter metabolism in vivo: on the correlation of total glucose consumption with glutamatergic action.
  23. (2001). Effects of anesthesia on functional activationofcerebralbloodflowand metabolism.
  24. (2003). Energy contribution of octanoatetointactratbrainmetabolism measured by 13C nuclear magneticresonancespectroscopy.J.Neurosci.
  25. (1999). Energy on demand.
  26. (2010). Evaluation of cerebral acetate transport and metabolic rates in the rat brain in vivo using 1H-[13C]-NMR.
  27. (2009). Exchange-mediated dilution of brain lactate specific activity: implications for the origin of glutamate dilution and the contributions of glutamine dilution and other pathways.
  28. (1993). Extracellular potassium regulates the glutamine content of astrocytes: mediation by intracellular pH.
  29. (2009). Fast isotopic exchange between mitochondria and cytosol in brain revealed by relayed 13C magnetization transfer spectroscopy.
  30. (2000). Field mapping without reference scan using asymmetric echo-planar techniques.
  31. (2003). Glycogen: the forgotten cerebral energy store.
  32. (2001). Glycolysis in neurons, not astrocytes, delays oxidative metabolism of human visual cortex during sustained checkerboard stimulation in vivo.
  33. (2010). In vivo neurochemical profiling of rat brain by 1H-[13C] NMR spectroscopy: cerebral energeticsandglutamatergic/GABAergic Frontiers
  34. (2004). Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain.
  35. (1996). Increased tricarboxylic acid cycle flux in rat brain during forepaw stimulation detected with 1H[13C]NMR.
  36. (1994). K(()-induced alkalinization in mouse cerebral astrocytes mediated by reversal of electrogenic Na(()-HCO3- cotransport.
  37. (2006). Localized short-echo-time proton MR spectroscopy with full signalintensity acquisition.
  38. (1996). Mathematical modelling of the citric acid cycle for the analysis of glutamine isotopomers from cerebellar astrocytes incubated with [1-13C]glucose.
  39. (2007). Mathematicalmodelingof 13Clabel incorporation of the TCA cycle: the concept of composite precursor function.
  40. (1996). Metabolism of [U-13C5] glutamine in cultured astrocytes studied by NMR spectroscopy: first evidence of astrocytic pyruvaterecycling.J.Neurochem.67,
  41. (2004). Neuroglial metabolism in the awake rat brain: CO2 fixation increases with brain activity.
  42. (1993). NMR spectroscopic studies of 13C acetate and 13C glucose metabolism in neocortical astrocytes: evidence for mitochondrial heterogeneity.
  43. (2002). Normalization of skeletal muscle glycogen synthesis and glycolysis in rosiglitazone-treated Zucker fatty rats: an in vivo nuclear magnetic resonance study.
  44. (2007). On the reliability of 13C metabolic modeling with two-compartment neuronalglial models.
  45. (1997). Oxidative glucose metabolism in rat brain during single forepaw stimulation: a spatially localized 1H[13C] nuclear magnetic resonance study.
  46. Propionate increases neuronal histone acetylation, but is metabolized oxidatively by glia. Relevance for propionic acidemia.
  47. R.,and Hutchinson,P.J.(2009).Thehuman brain utilizes lactate via the tricarboxylic acid cycle: a 13C-labelled microdialysis and high-resolution nuclear magnetic resonance study.
  48. (2004). Regional glucose metabolism and glutamatergic neurotransmission in rat brain in vivo.
  49. (2003). Regulation of glial metabolism studied by 13C-NMR.
  50. (1997). Role of pyruvate carboxylase in facilitation of synthesis of glutamate and glutamine in cultured astrocytes.
  51. (2011). Statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received:01April2011;accepted:17May 2011; published online: 06
  52. (2009). Steady-state brain glucose transport kinetics reevaluated with a four-state conformational model.
  53. (1994). stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization.
  54. (1998). Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity.
  55. (2007). Supply and demand in cerebral energy metabolism: the role of nutrient transporters.
  56. (2011). The case ofthemissingglutamine.NMR.Biomed. doi: 10.1002/nbm.1620. [Epub ahead of print].
  57. (2010). The contribution of blood lactate to brain energy metabolism in humans measured by dynamic 13C nuclear magnetic resonance spectroscopy.
  58. (2005). The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo.
  59. (2009). The in vivo neuron-to-astrocyte lactate shuttle in human brain: evidence from modeling of measured lactate levels during visual stimulation.
  60. (2003). Toward dynamic isotopomer analysis in the rat brain in vivo: automatic quantitation of 13C NMR spectra using LCModel.