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Astrocyte-Neuron Metabolic Pathways

Evidence Supporting the Existence of an Activity-Dependent Astrocyte-Neuron Lactate Shuttle

Pellerin L.a · Pellegri G.a · Bittar P.G.a · Charnay Y.b · Bouras C.b · Martin J.L.c · Stella N.c · Magistretti P.J.a

Author affiliations

a Institut de Physiologie, Université de Lausanne, and b Division de Neuropsychiatrie, IUPG Bel-Air, Université de Genève, Switzerland; c The Neurosciences Institute, San Diego, Calif., USA

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Dev Neurosci 1998;20:291–299

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Article / Publication Details

First-Page Preview
Abstract of Astrocyte-Neuron Metabolic Pathways

Published online: October 30, 1998
Issue release date: July – October 1998

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 1

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: https://www.karger.com/DNE

Abstract

Mounting evidence from in vitro experiments indicates that lactate is an efficient energy substrate for neurons and that it may significantly contribute to maintain synaptic transmission, particularly during periods of intense activity. Since lactate does not cross the blood-brain barrier easily, blood-borne lactate cannot be a significant source. In vitro studies by several laboratories indicate that astrocytes release large amounts of lactate. In 1994, we proposed a mechanism whereby lactate could be produced by astrocytes in an activity-dependent, glutamate-mediated manner. Over the last 2 years we have obtained further evidence supporting the notion that a transfer of lactate from astrocytes to neurons might indeed take place. In this article, we first review data showing the presence of mRNA encoding for two monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain. Second, by using monoclonal antibodies selectively directed against the two distinct lactate dehydrogenase isoforms, LDH1 and LDH5, a specific cellular distribution between neurons and astrocytes is revealed which suggests that a population of astrocytes is a lactate ‘source’ while neurons may be a lactate ‘sink’. Third, we provide biochemical evidence that lactate is interchangeable with glucose to support oxidative metabolism in cortical neurons. This set of data is consistent with the existence of an activity-dependent astrocyte-neuron lactate shuttle for the supply of energy substrates to neurons.


References

  1. Bishop MJ, Everse J, Kaplan NO: Identification of lactate dehydrogenase isoenzymes by rapid kinetics. Proc Natl Acad Sci USA 1972;69:1761–1765.
    External Resources
  2. Bittar PG, Charnay Y, Pellerin L, Bouras C, Magistretti PJ: Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain. J Cereb Blood Flow Metab 1996;16:1079–1089.
  3. Bröer S, Rahman B, Pellegri G, Pellerin L, Martin J-L, Verleysdonk S, Hamprecht B, Magistretti PJ: Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT 1) expressing Xenopus laevis oocytes. J Biol Chem 1997;272:30096–30102.
  4. Carpenter L, Poole RC, Halestrap AP: Cloning and sequencing of the monocarboxylate transporter from mouse Ehrlich Lettre tumour cell confirms its identity as MCT1 and demonstrates that glycosylation is not required for MCT1 function. Biochim Biophys Acta 1996;1279:157–163.
  5. Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ: Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 1979;18:5294–5299.
    External Resources
  6. Gerhart DZ, Enerson BE, Zhdankina OY, Leino R, Drewes LR (1997): Expression of the monocarboxylate transporter MCT1 by brain endothelium and glia in adult and suckling rats. Am J Physiol 1997;273:E207–213.
  7. Gerhart DZ, Enerson BE, Zhdankina OY, Leino RL, Drewes LR: Expression of the monocarboxylate transporter MCT2 by rat brain glia. Glia 1998;22:272–281.
  8. Gerhardt-Hansen W: Lactate dehydrogenase isoenzymes in the central nervous system. Dan Med Bull 1968;15:1–112.
    External Resources
  9. Hu Y, Wilson GS: A temporary local energy pool coupled to neuronal activity: Fluctuations of extracellular lactate levels in rat brain monitored with rapid-response enzyme-based sensor. J Neurochem 1997;69:1484–1490.
  10. Izumi Y, Benz AM, Katsuki H, Zorumski CF: Endogenous monocarboxylates sustain hippocampal synaptic function and morphological integrity during energy deprivation. J Neurosci 1997;17:9448–9457.
    External Resources
  11. Kim CM, Goldstein JL, Brown MS: cDNA cloning of MEV, a mutant protein that facilitates cellular uptake of mevalonate, and identification of the point mutation responsible for its gain of function. J Biol Chem 1992;267:23113–23121.
    External Resources
  12. Kim Garcia C, Goldstein JL, Pathak RK, Anderson RGW, Brown MS: Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: Implications for the Cori cycle. Cell 1994;76:865–873.
    External Resources
  13. Kim Garcia C, Brown MS, Pathak RK, Goldstein JL: cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different cells than MCT1. J Biol Chem 1995;270:1843–1849.
  14. Larrabee MG: Lactate metabolism and its effects on glucose metabolism in an excised neural tissue. J Neurochem 1995;64:1734–1741.
    External Resources
  15. McIlwain H: Substances which support respiration and metabolic response to electric impulses in human cerebral tissues. J Neurol Neurosurg Psychiatry 1953;16:257–266.
  16. McKenna MC, Tildon JT, Stevenson JH, Boatright R, Huang S: Regulation of energy metabolism in synaptic terminals and cultured rat brain astrocytes: Differences revealed using aminooxyacetate. Dev Neurosci 1993;15:320–329.
    External Resources
  17. McKenna MC, Tildon JT, Stevenson JH, Hopkins IB: Energy metabolism in cortical synaptic terminals from weanling and mature rat brain: Evidence for multiple compartments of tricarboxylic acid cycle activity. Dev Neurosci 1994;16:291–300.
    External Resources
  18. Morgello S, Uson RR, Schwartz EJ, Haber RS: The human blood-brain barrier glucose transporter (GLUT1) is a glucose transporter of gray matter astrocytes. Glia 1995;14:43–54.
    External Resources
  19. Nedergaard M, Goldman SA: Carrier-mediated transport of lactic acid in cultured neurons and astrocytes. Am J Physiol 1993;265:R282–R289.
    External Resources
  20. Pardridge WM, Oldendorf WH: Transport of metabolic substrates through the blood-brain barrier. J Neurochem 1977;28:5–12.
    External Resources
  21. Pellerin L, Magistretti PJ: Glutamate uptake into astrocytes stimulates aerobic glycolysis: A mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci USA 1994;91:10625–10629.
  22. Pellerin L, Magistretti PJ: Excitatory amino acids stimulate aerobic glycolysis in astrocytes via an activation of the Na+/K+-ATPase. Dev Neurosci 1996;18:336–342.
  23. Pellerin L, Magistretti PJ: Glutamate uptake stimulates Na+,K+-ATPase activity in astrocytes via activation of a distinct subunit highly sensitive to ouabain. J Neurochem 1997;69:2132–2137.
    External Resources
  24. Pellerin L, Pellegri G, Martin J-L, Magistretti PJ: Expression of monocarboxylate transporter
  25. mRNAs in mouse brain: Support for a distinct role of lactate as an energy substrate for the neonatal vs adult brain. Proc Natl Acad Sci USA 1998;95:3990–3995.
  26. Philp N, Chu P, Pan T-C, Zhang RZ, Chu M-L, Stark K, Boettiger D, Yoon H, Kieber-Emmons T: Developmental expression and molecular cloning of REMP, a novel retinal epithelial membrane protein. Exp Cell Res 1995;219:64–73.
  27. Poitry-Yamate CL, Poitry S, Tsacopoulos M: Lactate released by Müller glial cells is metabolized by photoreceptors from mammalian retina. J Neurosci 1995;15:5179–5191.
  28. Schurr A, West CA, Rigor BM: Lactate-supported synaptic function in the rat hippocampal slice preparation. Science 1988;240:1326–1328.
  29. Schurr A, Payne RS, Miller JJ, Rigor BM: Brain lactate is an obligatory aerobic energy substrate for functional recovery after hypoxia: Further in vitro validation. J Neurochem 1997;69:423–426.
    External Resources
  30. Sibson NR, Dhankhar A, Mason GF, Rothman DL, Behar KL, Shulman RG: Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. Proc Natl Acad Sci USA 1998;95:316–321.
  31. Slater TF, Sawyer B, Sträuli U: Studies on succinate-tetrazolium reductase systems. Biochim Biophys Acta 1963;77:383–393.
  32. Stella N, Pellerin L, Magistretti PJ: Modulation of the glutamate-evoked release of arachidonic acid from mouse cortical neurons: Involvement of a pH-sensitive membrane phospholipase A2. J Neurosci 1995;15:3307–3317.
  33. Tildon JT, McKenna MC, Stevenson J, Couto R: Transport of L-lactate by cultured rat brain astrocytes. Neurochem Res 1993;18:177–184.
    External Resources
  34. Tsacopoulos M, Magistretti PJ: Metabolic coupling between glia and neurons. J Neurosci 1996;16:877–885.
  35. Waagepetersen HS, Bakken IJ, Larsson OM, Sonnewald U, Schousboe A (1998) Metabolism of lactate in cultured GABAergic neurons studied by 13C nuclear magnetic resonance spectroscopy. J Cereb Blood Flow Metab 1998;18:109–117.
  36. Walz W, Mukerji S: Lactate production and release in cultured astrocytes. Neurosci Lett 1988;86:296–300.
  37. Yoon H, Fanelli A, Grollman EF, Philp NJ: Identification of a unique monocarboxylate transporter (MCT3) in retinal pigment epithelium. Biochem Biophys Res Commun 1997;234:90–94.

Article / Publication Details

First-Page Preview
Abstract of Astrocyte-Neuron Metabolic Pathways

Published online: October 30, 1998
Issue release date: July – October 1998

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 1

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: https://www.karger.com/DNE


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