Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

13C-MRS studies on cerebral metabolism

  • 18 Accesses

  • 6 Citations

Abstract

13C from labeled glucose is normally incorporated rapidly into cerebral glutamate with little detectable glutamine or citrate. In contrast, glutamine and citrate only show significant labeling from13C acetate, which reflects metabolism in glial cells. When brain slices are depolarized with 40 mM KC1 (which mirrors some of the conditions of epilepsy) the13C enrichment of glutamine and citrate from glucose is accelerated in contrast to that of glutamate, which is not. This clearly indicates that depolarizing conditions stimulate glial rather than neuronal consumption of glucose.

In tissues subjected to hypoxia, there is greatly increased labeling of glycerol 3-phosphate, which was confirmed by its increased presence in31P-MR (magnetic resonance) spectra. Analysis of the labeling of lactate, alanine, and glycerol 3-phosphate demonstrated that the ability of the brain to maintain normal function in hypoxia is limited by the capacity of the key enzyme, lactate dehydrogenase. This has implications in the clinical assessment and management of stroke. These results also have implications in the interpretation of activation studies, where increased lactate could be due either to depolarization or hypoxia, or both.

The spectra observed in studies on metabolism of U-[13C] glutamate in cerebral preparations revealed clear signals from glutamine and lactate released to the media. The isotopomer patterns of the lactate showed that it must have arisen from the exogenous glutamate, because if it were due to naturally abundant13C in the lactate, only singlets would have appeared. Comparison of the isotopomer patterns and the percentage13C enrichments of the glutamine and lactate showed that there is higher incorporation of13C from exogenous glutamate into lactate than into glutamine. The enrichment of the lactate indicated that very little was derived from glucose and suggests that the glutamate is converted to lactate in the glia for use by the neurones.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Badar-Goffer RS, Bachelard HS, Morris PG (1990) Cerebral metabolism of acetate and glucose studied by13C-NMR spectroscopy: a technique for investigating metabolic compartmentation in the brain.Biochem J 266 133–139.

  2. 2.

    Badar-Goffer RG, Ben-Yoseph O, Bachelard HS, Morris PG (1992) Neuronal-glial metabolism under depolarizing conditions—a13C-n.m.r. study.Biochem J 282 225–230.

  3. 3.

    Ben-Yoseph O, Badar-Goffer RS, Morris PG, Bachelard HS (1993) Glycerol 3-phosphate and lactate as indicators of the cerebral cytoplasmic redox state in severe and mild hypoxia respectively: a13C- and31P-NMR study.Biochem J 291 915–919.

  4. 4.

    Bachelard HS, Badar-Goffer RS, Brooks KJ, Dolin SJ, Morris PG (1988) Measurement of free intracellular calcium in the brain by19F-nuclear magnetic resonance spectroscopy.J Neurochem 51 1311–1313.

  5. 5.

    Mcllwain H, Bachelard HS (1985)Biochemistry and the Central Nervous System, 5th ed. Edinburgh: Churchill-Livingstone.

  6. 6.

    Bachelard HS, Badar-Goffer RS (1993) NMR spectroscopy in neurochemistry.J Neurochem 61 412–429.

  7. 7.

    Sonnewald U, Westergaard N, Petersen SB, Unsgard G, Schousboe A (1993) Metabolism of [U-13 C] glutamate in astrocytes studied by13C NMR spectroscopy: incorporation of more label into lactate than into glutamine demonstrates the importance of the tricarboxylic acid cycle.J Neurochem 61 1179–1182.

  8. 8.

    Prichard J, Rothman D, Novotny E, Petroff O, Avison M, Howseman A, Hanstock C, Shulman R (1989) Photic stimulation raises lactate in human visual cortex [Abstract].Proceedings of the 8th Annual Meeting, Society of Magnetic Resonance in Medicine, p. 1071.

  9. 9.

    Garafola O, Cox DWG, Bachelard HS (1988) Brain levels of NADH and NAD+ under hypoxic and hypoglycaemic conditions in vitro.J Neurochem 51 172–176.

Download references

Author information

Correspondence to Herman Bachelard.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bachelard, H., Badar-Goffer, R., Ben-Yoseph, O. et al. 13C-MRS studies on cerebral metabolism. MAGMA 2, 285–289 (1994). https://doi.org/10.1007/BF01705254

Download citation

Keywords

  • Glucose
  • Lactate
  • Citrate
  • Glutamate
  • Glutamine