Neuroenergetics: Calling upon Astrocytes to Satisfy Hungry Neurons

Neuroscientist

Volumn 10, Issue 1, 2004, Pages 53-62

  Pellerin, Luc ^a,b   Magistretti, Pierre J ^a  

^a UNIVERSITY OF LAUSANNE   (Switzerland)

^b UNIVERSITY OF LAUSANNE   (Switzerland)

Author keywords

Aerobic glycolysis; Brain energy metabolism; Glucose; Lactate; Monocarboxylate transporters

Indexed keywords

GLUCOSE; LACTIC ACID;

ASTROCYTE; BRAIN METABOLISM; ENERGY METABOLISM; ENERGY TRANSFER; GLIA CELL; GLYCOLYSIS; OXIDATION; PRIORITY JOURNAL; REVIEW;

ANIMALS; ASTROCYTES; ENERGY METABOLISM; HUMANS; NEURODEGENERATIVE DISEASES; NEURONS;

EID: 1642457265     PISSN: 10738584     EISSN: None     Source Type: Journal    
DOI: 10.1177/1073858403260159     Document Type: Review

References (100)

1. + channels. J Physiol (Lond) 544:429-45.
2. Attwell D, Laughlin SB. 2001. An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab 21:1133-45.
3. Bergersen L, Johansson E, Veruki ML, Nagelhus EA, Halestrap AP, Sejersted OM, and others. 1999. Cellular and subcellular expression of monocarboxylate transporters in the pigment epithelium and retina of the rat. Neuroscience 90:319-31.
4. Bergersen L, Waerhaug O, Helm J, Thomas M, Laake P, Davies AJ, and others. 2001. A novel postsynaptic density protein: the monocarboxylate transporter MCT2 is co-localized with δ-glutamate receptors in postsynaptic densities of parallel fiber-Purkinje cell synapses. Exp Brain Res 136:523-34.
5. Bittar PG, Charnay Y, Pellerin L, Bouras C, Magistretti PJ. 1996. Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain. J Cereb Blood Flow Metab 16:1079-89.
6. Bonvento G, Sibson N, Pellerin L. 2002. Does glutamate image your thoughts? Trends Neurosci 25:359-64.
7. Boussouar F, Mauduit C, Tabone E, Pellerin L, Magistretti PJ, Benhamed M. 2003. Developmental and hormonal regulation of the monocarboxylate transporter 2 (MCT2) expression in the mouse germ cells. Biol Reprod 69:1069-78.
8. Bouzier AK, Thiaudiere E, Biran M, Rouland R, Canioni P, Merle M. 2000. The metabolism of [3-(13)C] lactate in the rat brain is specific of a pyruvate carboxylase-deprived compartment. J Neurochem 75:480-6.
9. Bouzier-Sore AK, Merle M, Magistretti PJ, Pellerin L. 2002. Feeding active neurons: (re)emergence of a nursing role for astrocytes. J Physiol (Paris) 96:273-82.
10. Bouzier-Sore AK, Voisin P, Canioni P, Magistretti PJ, Pellerin L. 2003. Lactate is a preferential oxidative energy substrate over glucose for neurons in culture. J Cereb Blood Flow Metab 23:1298-1306.
11. Bröer S, Rahman B, Pellegri G, Pellerin L, Martin JL, Verleysdonk S, and others. 1997. Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT1) expressing Xenopus laevis oocytes: expression of two different monocarboxylate transporters in astroglial cells and neurons. J Biol Chem 272:30096-102.
12. Brooks GA 2002. Lactate shuttles in nature. Biochem Soc Trans 30:258-64.
13. Brown AM, Tekkok SB, Ransom BR. 2003. Glycogen regulation and functional role in mouse white matter. J Physiol (Lond) 549:501-12.
14. Casale CH, Previtali G, Barra HS. 2003. Involvement of acetylated tubulin in the regulation of Na+,K+-ATPase activity in cultured astrocytes. FEBS Lett 534:115-8.
15. Cater HL, Benham CD, Sundstrom LE. 2001. Neuroprotective role of monocarboxylate transport during glucose deprivation in slice cultures of rat hippocampus. J Physiol 531:459-66.
16. Chatton JY, Marquet P, Magistretti PJ. 2000. A quantitative analysis of L-glutamate-regulated Na+ dynamics in mouse cortical astrocytes: implications for cellular bioenergetics. Eur J Neurosci 12:3843-53.
17. Chatton JY, Pellerin L, Magistretti PJ. 2003. GABA uptake into astrocytes is not associated with significant metabolic cost: implications for brain imaging of inhibitory transmission. Proc Natl Acad Sci U S A 100:12456-61.
18. Choi IY, Seaquist ER, Gruetter R. 2003. Effect of hypoglycemia on brain glycogen metabolism in vivo. J Neurosci Res 72:25-32.
19. Cholet N, Pellerin L, Magistretti PJ, Hamel E. 2002. Similar perisynaptic glial localization for the Na+,K+-ATPase alpha 2 subunit and the glutamate transporters GLAST and GLT-1 in the rat somatosensory cortex. Cereb Cortex 12:515-25.
20. Cholet N, Pellerin L, Welker E, Lacombe P, Seylaz J, Magistretti P, and others. 2001. Local injection of antisense oligonucleotides targeted to the glial glutamate transporter GLAST decreases the metabolic response to somatosensory activation. J Cereb Blood Flow Metab 21:404-12.
21. Debernardi R, Pierre K, Lengacher S, Magistretti PJ, Pellerin L. 2003. Cell-specific expression pattern of monocarboxylate transporters in astrocytes and neurons observed in different mouse brain cortical cell cultures. J Neurosci Res 73:141-55.
22. Drewes LR. 2003. Molecular features, regulation, and function of monocarboxylate transporters: implications for drug delivery. J Pharm Sci 92:1531-44.
23. Dringen R, Gebhardt R, Hamprecht B. 1993. Glycogen in astrocytes: possible function as lactate supply for neighboring cells. Brain Res 623:208-14.
24. 13C nuclear magnetic resonance spectroscopy. J Neurosci 23:5928-35.
25. Fellows LK, Boutelle MG, Fillenz M. 1993. Physiological stimulation increases nonoxidative glucose metabolism in the brain of the freely moving rat. J Neurochem 60:1258-63.
26. Fernandez E, Medina JM. 1986. Lactate utilization by the neonatal rat brain in vitro. Competition with glucose and 3-hydroxybutyrate. Biochem J 234:489-92.
27. Fowler JC. 1993. Glucose deprivation results in a lactate preventable increase in adenosine and depression of synaptic depression in rat hippocampal slices. J Neurochem 60:572-6.
28. Gerhart DZ, Enerson BE, Zhdankina OY, Leino RL, Drewes LR. 1997. Expression of monocarboxylate transporter MCT1 by brain endothelium and glia in adult and suckling rats. Am J Physiol 273:E207-13.
29. Gerhart DZ, Enerson BE, Zhdankina OY, Leino RL, Drewes LR. 1998. Expression of the monocarboxylate transporter MCT2 by rat brain glia. Glia 22:272-81.
30. Guzman M, Blazquez C. 2001. Is there an astrocyte-neuron ketone body shuttle? Trends Endocrinol Metab 12:169-73.
31. Halestrap AP, Meredith D. 2003. The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Eur J Physiol (in press).
32. Hanu R, McKenna M, O'Neill A, Resneck WG, Bloch RJ. 2000. Monocarboxylic acid transporters, MCT1 and MCT2, in cortical astrocytes in vitro and in vivo. Am J Physiol 278:C921-30.
33. Hassel B, Brathe A. 2000. Cerebral metabolism of lactate in vivo: evidence for neuronal pyruvate carboxylation. J Cereb Blood Flow Metab 20:327-36.
34. Himmi T, Perrin J, Dallaporta M, Orsini JC. 2001. Effects of lactate on glucose-sensing neurons in the solitary tract nucleus. Physiol Behav 74:391-7.
35. Honegger P, Braissant O, Henry H, Boulat O, Bachmann C, Zurich MG, and others. 2002. Alteration of amino acid metabolism in neuronal aggregate cultures exposed to hypoglycaemic conditions. J Neurochem 81:1141-51.
36. Hu Y, Wilson GS. 1997. 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 69:1484-90.
37. Ide K, Horn A, Secher NH. 1999. Cerebral metabolic response to submaximal exercise. J Appl Physiol 87:1604-8.
38. 2 uptake in human brain during recovery from maximal exercise. J Physiol 522:159-64.
39. Ide T, Steinke J, Cahill GF Jr. 1969. Metabolic interactions of glucose, lactate, and β-hydroxybutyrate in rat brain slices. Am J Physiol 217:784-92.
40. Itoh Y, Esaki T, Shimoji K, Cook M, Law MJ, Kaufman E, and others. 2003. Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo. Proc Natl Acad Sci U S A 100:4879-84.
41. Izumi Y, Benz AM, Katsuki H, Zorumski CE 1997. Endogenous monocarboxylates sustain hippocampal synaptic function and morphological integrity during energy deprivation. J Neurosci 17:9448-57.
42. Izumi Y, Benz AM, Zorumski CF, Olney JW. 1994. Effects of lactate and pyruvate on glucose utilization in rat hippocampal slices. Neuroreport 5:617-20.
43. Izumi Y, Katsuki H, Zorumski CF. 1997. Monocarboxylates (pyruvate and lactate) as alternative energy substrates for the induction of long-term potentiation in rat hippocampal slices. Neurosci Lett 232:17-20.
44. Jackson VN, Price NT, Carpenter L, Halestrap AP. 1997. Cloning of the monocarboxylate transporter isoform MCT2 from rat testis provides evidence that expression in tissues is species-specific and may involve post-transcriptional regulation. Biochem J 324:447-53.
45. Juel C, Halestrap AP. 1999. Lactate transport in skeletal muscle-role and regulation of the monocarboxylate transporter. J Physiol (Lond) 517:633-42.
46. King P, Kong MF, Parkin H, MacDonald IA, Barber C, Tattersall RB. 1998. Intravenous lactate prevents cerebral dysfunction during hypoglycemia in insulin-dependent diabetes mellitus. Clin Sci 94:157-63.
47. Koehler-Stec EM, Simpson IA, Vannucci SJ, Landschulz KT, Landschulz WH. 1998. Monocarboxylate transporter expression in mouse brain. Am J Physiol 275:E516-24.
48. Larrabee MG. 1983. Lactate uptake and release in the presence of glucose by sympathetic ganglia of chicken embryos and by neuronal and nonneuronal cultures prepared from these ganglia. J Neurochem 40:1237-50.
49. Larrabee MG. 1992. Extracellular intermediates of glucose metabolism: fluxes of endogenous lactate and alanine through extracellular pools in embryonic sympathetic ganglia. J Neurochem 59:1041-52.
50. Larrabee MG. 1995. Lactate metabolism and its effect on glucose metabolism in an excised neural tissue. J Neurochem 64:1734-41.
51. Larrabee MG. 1996. Partitioning of CO2 production between glucose and lactate in excised sympathetic ganglia, with implications for brain. J Neurochem 67:1726-34.
52. Laughton JD, Charnay Y, Belloir B, Pellerin L, Magistretti PJ, Bouras C. 2000. Differential messenger RNA distribution of lactate dehydrogenase LDH-1 and LDH-5 isoforms in the rat brain. Neuroscience 96:619-25.
53. Leino RL, Gerhart DZ, Drewes LR. 1999. Monocarboxylate transporter (MCT1) abundance in brains of suckling and adult rats: a quantitative electron microscopic immunogold study. Dev Brain Res 113:47-54.
54. Leino RL, Gerhart DZ, Duelli R, Enerson BE, Drewes LR. 2001. Diet-induced ketosis increases monocarboxylate transporter (MCT1) levels in rat brain. Neurochem Int 38:519-27.
55. Loaiza A, Porras OH, Barros LE 2003. Glutamate triggers rapid glucose transport stimulation in astrocytes as evidenced by real-time confocal microscopy. J Neurosci 23:7337-42.
56. Magistretti PJ, Pellerin L. 1999. Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Phil Trans Roy Soc Lond B Biol Sci 354:1155-63.
57. Magistretti PJ, Sorg O, Martin JL. 1993. Regulation of glycogen metabolism in astrocytes: physiological, pharmacological, and pathological aspects. In: Murphy S, editor. Astrocytes: pharmacology and function. New York: Academic Press. p 243-65.
58. Maher F, Vannucci SJ, Simpson IA. 1994. Glucose transporter proteins in brain. FASEB J 8:1003-11.
59. Maran A, Cranston I, Lomas J, Macdonald I, Amiel SA. 1994. Protection by lactate of cerebral function during hypoglycemia. Lancet 343:16-20.
60. Maran A, Crepaldi C, Trupiani S, Lucca T, Jori E, Macdonald IA, and others. 2000. Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and type I diabetic subjects. Diabetologia 43:733-41.
61. McKenna MC, Hopkins IB, Carey A. 2001. α-cyano-4-hydroxycinnamate decreases both glucose and lactate metabolism in neurons and astrocytes: implications for lactate as an energy substrate for neurons. J Neurosci Res 66:747-54.
62. McKenna MC, Tildon JT, Stevenson JH, Boatright R, Huang S. 1993. Regulation of energy metabolism in synaptic terminals and cultured rat brain astrocytes: differences revealed using aminooxyacetate. Dev Neurosci 15:320-9.
63. McKenna MC, Tildon JT, Stevenson JH, Hopkins IB. 1994. Energy metabolism in cortical synaptic terminals from weanling and mature rat brain: evidence for multiple compartments of tricarboxylic acid cycle activity. Dev Neurosci 16:291-300.
64. McKenna MC, Tildon JT, Stevenson JH, Hopkins IB, Huang X, Couto R. 1998. Lactate transport by cortical synaptosomes from adult brain: characterization of kinetics and inhibitor specificity. Dev Neurosci 20:300-9.
65. Mobbs CV, Kow LM, Yang XJ. 2001. Brain glucose-sensing mechanisms: ubiquitous silencing by aglycemia vs. hypothalamic neuroendocrine responses. Am J Physiol 281:E649-54.
66. Nehlig A, Pereira de Vasconcelos A. 1993. Glucose and ketone body utilization by the brain of neonatal rats. Prog Neurobiol 40:163-221.
67. Pellerin L. 2003. Lactate as a pivotal element in neuron-glia metabolic cooperation. Neurochem Int 43:331-8.
68. Pellerin L, Magistretti PJ. 1994. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A 91:10625-9.
69. Pellerin L, Magistretti PJ. 1997. Glutamate uptake stimulates Na+,K+-ATPase activity in astrocytes via activation of a distinct subunit highly sensitive to ouabain. J Neurochem 69:2132-7.
70. Pellerin L, Magistretti PJ. 2003. How to balance the brain energy budget while spending glucose differently. J Physiol (Lond) 546:325.
71. Pellerin L, Pellegri G, Bittar PG, Charnay Y, Bouras C, Martin JL, and others. 1998. Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle. Dev Neurosci 20:291-9.
72. Pellerin L, Pellegri G, Martin JL, Magistretti PJ. 1998. Expression of monocarboxylate transporter 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 U S A 95:3990-5.
73. Pierre K, Debernardi R, Magistretti PJ, Pellerin L. 2003. Noradrenaline enhances monocarboxylate transporter 2 expression in cultured mouse cortical neurons via a translational regulation. J Neurochem 86:1468-76.
74. Pierre K, Magistretti PJ, Pellerin L. 2002. MCT2 is a major neuronal monocarboxylate transporter in the adult mouse brain. J Cereb Blood Flow Metab 22:586-95.
75. Pierre K, Pellerin L, Debemardi R, Riederer BM, Magistretti PJ. 2000. Cell-specific localization of monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain revealed by double immunohistochemical labeling and confocal microscopy. Neuroscience 100:617-27.
76. Poitry-Yamate CL, Poitry S, Tsacopoulos M. 1995. Lactate released by Muller glial cells is metabolized by photoreceptors from mammalian retina. J Neurosci 15:5179-91.
77. Qu H, Haberg A, Haraldseth O, Unsgard G, Sonnewald U. 2000. (13)C MR spectroscopy study of lactate as substrate for rat brain. Dev Neurosci 22:429-36.
78. Rafiki A, Boulland JL, Halestrap AP, Ottersen OP, Bergersen L. 2003. Highly differential expression of the monocarboxylate transporters MCT2 and MCT4 in the developing rat brain. Neuroscience 122:677-88.
79. Schousboe A, Westergaard N, Waagepetersen HS, Larsson OM, Bakken IJ, Sonnewald U. 1997. Trafficking between glia and neurons of TCA cycle intermediates and related metabolites. Glia 21:99-105.
80. Schurr A, Miller JJ, Payne RS, Rigor BM. 1999. An increase in lactate output by brain tissue serves to meet the energy needs of glutamate-activated neurons. J Neurosci 19:34-39.
81. Schurr A, West CA, Rigor BM. 1988. Lactate-supported synaptic function in the rat hippocampal slice preparation. Science 240:1326-8.
82. Smith D, Pernet A, Hallett WA, Bingham E, Marsden PK, Amiel SA. 2003. Lactate: a preferred fuel for human brain metabolism in vivo. J Cereb Blood Flow Metab 23:658-64.
83. Sokoloff L. 1989. Circulation and energy metabolism of the brain. In: Siegel G, Agranoff B, Albers RW, Molinoff P, editors. Basic neurochemistry. 4th ed. New York: Raven Press. p 565-90.
84. Swanson RA, Morton MM, Sagar SM, Sharp FR. 1992. Sensory stimulation induces local cerebral glycogenolysis: demonstration by autoradiography. Neuroscience 51:451-61.
85. Tabernero A, Vicario C, Medina JM. 1996. Lactate spares glucose as a metabolic fuel in neurons and astrocytes from primary culture. Neurosci Res 26:369-76.
86. Thurston JH, Hauhart RE. 1989. Effect of momentary stress on brain energy metabolism in weanling mice: apparent use of lactate as cerebral metabolic fuel concomitant with a decrease in brain glucose utilization. Metab Brain Dis 4:177-86.
87. Tsacopoulos M, Evequoz-Mercier V, Perrottet P, Buchner E. 1988. Honeybee retinal glial cells transform glucose and supply the neurons with metabolic substrate. Proc Natl Acad Sci U S A 85:8727-31.
88. Tsacopoulos M, Veuthey AL, Saravelos SG, Perrottet P, Tsoupras G. 1994. Glial cells transform glucose to alanine, which fuels the neurons in the honeybee retina. J Neurosci 14:1339-51.
89. Véga C, Martiel JL, Drouhault D, Burckhart MF, Coles JA. 2003. Uptake of locally applied deoxyglucose, glucose and lactate by axons and Schwann cells of rat vagus nerve. J Physiol 546:551-64.
90. Véga C, Poitry-Yamate CL, Jirounek P, Tsacopoulos M, Coles JA. 1998. Lactate is released and taken up by isolated rabbit vagus nerve during aerobic metabolism. J Neurochem 71:330-7.
91. Vicario C, Arizmendi C, Malloch G, Clark JB, Medina JM. 1991. Lactate utilization by isolated cells from early neonatal rat brain. J Neurochem 57:1700-7.
92. Voutsinos-Porche B, Bonvento G, Tanaka K, Steiner P, Welker E, Chatton JY, and others. 2003. Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex. Neuron 37:275-86.
93. Voutsinos-Porche B, Knott G, Tanaka K, Quairiaux C, Welker E, Bonvento G. 2003. Glial glutamate transporters and maturation of the mouse somatosensory cortex. Cereb Cortex 13:1110-21.
94. Waagepetersen HS, Bakken IJ, Larsson OM, Sonnewald U, Schousboe A. 1998. Comparison of lactate and glucose metabolism in cultured neocortical neurons and astrocytes using 13C-NMR spectroscopy. Dev Neurosci 20:310-20.
95. Waagepetersen HS, Sonnewald U, Larsson OM, Schousboe A. 2000. A possible role of alanine for ammonia transfer between astrocytes and glutamatergic neurons. J Neurochem 75:471-9.
96. Waldvogel D, van Gelderen P, Muellbacher W, Ziemann U, Immisch I, Hallett M. 2000. The relative metabolic demand of inhibition and excitation. Nature 406:995-8.
97. Walz W, Mukerji S. 1988. Lactate release from cultured astrocytes and neurons: a comparison. Glia 1:366-70.
98. 14C]2-deoxyglucose by neurons and astrocytes. J Trace Microprobe Tech 20:505-15.
99. Zonta M, Angulo MC, Gobbo S, Rosengarten B, Hossmann KA, Pozzan T, and others. 2003. Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nature Neurosci 6:43-50.
100. Zwingmann C, Richter-Landsberg C, Brand A Leibfritz D. 2000. NMR spectroscopic study on the metabolic fate of [3-(13)C]alanine in astrocytes, neurons, and cocultures: implications for glia-neuron interactions in neurotransmitter metabolism. Glia 32:286-303.