Is L-lactate a novel signaling molecule in the brain?

Journal of Cerebral Blood Flow and Metabolism

Volumn 35, Issue 7, 2015, Pages 1069-1075

  Mosienko, Valentina ^a   Teschemacher, Anja G ^a   Kasparov, Sergey ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

astrocytes; ATP; brain slice; lactate; optogenetics

Indexed keywords

ADENOSINE TRIPHOSPHATE; ADENOSINE TRIPHOSPHATE SENSITIVE POTASSIUM CHANNEL; G PROTEIN COUPLED RECEPTOR; GPR81 PROTEIN, HUMAN; LACTIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR;

ANIMAL; ASTROCYTE; BRAIN; CYTOLOGY; HUMAN; METABOLISM; SIGNAL TRANSDUCTION;

ADENOSINE TRIPHOSPHATE; ANIMALS; ASTROCYTES; BRAIN; HUMANS; KATP CHANNELS; LACTIC ACID; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, N-METHYL-D-ASPARTATE; SIGNAL TRANSDUCTION;

EID: 84934441936     PISSN: 0271678X     EISSN: 15597016     Source Type: Journal    
DOI: 10.1038/jcbfm.2015.77     Document Type: Review

References (80)

1. Dienel GA. Brain lactate metabolism: the discoveries and the controversies. J Cereb Blood Flow Metab 2012; 32: 1107-1138
2. Dienel GA. Fueling and imaging brain activation. ASN Neuro 2012; 4: 5
3. Boumezbeur F, Petersen KF, Cline GW, Mason GF, Behar KL, Shulman GI, et al. The contribution of blood lactate to brain energy metabolism in humans measured by dynamic 13C nuclear magnetic resonance spectroscopy. J Neurosci 2010; 30: 13983-13991
4. Ross JM, Oberg J, Brene S, Coppotelli G, Terzioglu M, Pernold K, et al. High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio. Proc Natl Acad Sci USA 2010; 107: 20087-20092
5. Fujishima M, Sugi T, Morotomi Y, Omae T. Effects of bilateral carotid artery ligation on brain lactate and pyruvate concentrations in normotensive and spontaneously hypertensive rats. Stroke 1975; 6: 62-66
6. Mangia S, Tkac I, Gruetter R, Van de Moortele PF, Maraviglia B, Ugurbil K. Sustained neuronal activation raises oxidative metabolism to a new steady-state level: evidence from 1H NMR spectroscopy in the human visual cortex. J Cereb Blood Flow Metab 2007; 27: 1055-1063
7. Smith ML, von Hanwehr R, Siesjo BK. Changes in extra-And intracellular pH in the brain during and following ischemia in hyperglycemic and in moderately hypoglycemic rats. J Cereb Blood Flow Metab 1986; 6: 574-583
8. Harada M, Okuda C, Sawa T, Murakami T. Cerebral extracellular glucose and lactate concentrations during and after moderate hypoxia in glucose-And salineinfused rats. Anesthesiology 1992; 77: 728-734
9. Kuhr WG, Korf J. Extracellular lactic acid as an indicator of brain metabolism: continuous on-line measurement in conscious, freely moving rats with intrastriatal dialysis. J Cereb Blood Flow Metab 1988; 8: 130-137
10. Lin B, Busto R, Globus MY, Martinez E, Ginsberg MD. Brain temperature modulations during global ischemia fail to influence extracellular lactate levels in rats. Stroke 1995; 26: 1634-1638
11. Fray AE, Forsyth RJ, Boutelle MG, Fillenz M. The mechanisms controlling physiologically stimulated changes in rat brain glucose and lactate: a microdialysis study. J Physiol 1996; 496: 49-57
12. Demestre M, Boutelle M, Fillenz M. Stimulated release of lactate in freely moving rats is dependent on the uptake of glutamate. J Physiol 1997; 499: 825-832
13. Sotelo-Hitschfeld T, Niemeyer MI, Machler P, Ruminot I, Lerchundi R, Wyss MT, et al. Channel-mediated lactate release by k+-stimulated astrocytes. J Neurosci 2015; 35: 4168-4178
14. San Martin A, Ceballo S, Ruminot I, Lerchundi R, Frommer WB, Barros LF. A genetically encoded FRET lactate sensor and its use to detect the Warburg effect in single cancer cells. PLoS One 2013; 8: e57712
15. Goodman JC, Valadka AB, Gopinath SP, Uzura M, Robertson CS. Extracellular lactate and glucose alterations in the brain after head injury measured by microdialysis. Crit Care Med 1999; 27: 1965-1973
16. Reinstrup P, Stahl N, Mellergard P, Uski T, Ungerstedt U, Nordstrom CH. Intracerebral microdialysis in clinical practice: baseline values for chemical markers during wakefulness, anesthesia, and neurosurgery. Neurosurgery 2000; 47: 701-709, discussion 709-10
17. Bergersen LH. Is lactate food for neurons? Comparison of monocarboxylate transporter subtypes in brain and muscle. Neuroscience 2007; 145: 11-19
18. Gladden LB. Lactate metabolism: a new paradigm for the third millennium. J Physiol 2004; 558: 5-30
19. Verkhratsky A, Butt A. Glial Neurobiology. John Wiley & Sons, Ltd.: Chichester, England, 2007
20. Dringen R, Wiesinger H, Hamprecht B. Uptake of L-lactate by cultured rat brain neurons. Neurosci Lett 1993; 163: 5-7
21. Magistretti PJ, Sorg O, Yu N, Martin JL, Pellerin L. Neurotransmitters regulate energy metabolism in astrocytes: implications for the metabolic trafficking between neural cells. Dev Neurosci 1993; 15: 306-312
22. Pellerin L, Pellegri G, Bittar PG, Charnay Y, Bouras C, Martin JL, et al. Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle. Dev Neurosci 1998; 20: 291-299
23. Matsui T, Ishikawa T, Ito H, Okamoto M, Inoue K, Lee MC, et al. Brain glycogen supercompensation following exhaustive exercise. J Physiol 2012; 590: 607-616
24. Oz G, Kumar A, Rao JP, Kodl CT, Chow L, Eberly LE, et al. Human brain glycogen metabolism during and after hypoglycemia. Diabetes 2009; 58: 1978-1985
25. 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
26. Gandhi GK, Cruz NF, Ball KK, Dienel GA. Astrocytes are poised for lactate trafficking and release from activated brain and for supply of glucose to neurons. J Neurochem 2009; 111: 522-536
27. Quistorff B, Grunnet N. High brain lactate is not caused by a shift in the lactate dehydrogenase A/B ratio. Proc Natl Acad Sci USA 2011; 108: E21
28. Quistorff B, Grunnet N. The isoenzyme pattern of LDH does not play a physiological role; except perhaps during fast transitions in energy metabolism. Aging 2011; 3: 457-460
29. Hawkins RA, Miller AL, Nielsen RC, Veech RL. The acute action of ammonia on rat brain metabolism in vivo. Biochem J 1973; 134: 1001-1008
30. Takanaga H, Tamai I, Inaba S, Sai Y, Higashida H, Yamamoto H, et al. cDNA cloning and functional characterization of rat intestinal monocarboxylate transporter. Biochem Biophys Res Commun 1995; 217: 370-377
31. Price NT, Jackson VN, Halestrap AP. Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past. Biochem J 1998; 329: 321-328
32. Garcia CK, 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
33. Garcia CK, Goldstein JL, Pathak RK, Anderson RG, Brown MS. Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle. Cell 1994; 76: 865-873
34. Manning Fox JE, Meredith D, Halestrap AP. Characterisation of human monocarboxylate transporter 4 substantiates its role in lactic acid efflux from skeletal muscle. J Physiol 2000; 529: 285-293
35. 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
36. Bergersen L, Waerhaug O, Helm J, Thomas M, Laake P, Davies AJ, et al. A novel postsynaptic density protein: the monocarboxylate transporter MCT2 is colocalized with delta-glutamate receptors in postsynaptic densities of parallel fiber-Purkinje cell synapses. Exp Brain Res 2001; 136: 523-534
37. Rafiki A, Boulland JL, Halestrap AP, Ottersen OP, Bergersen L. Highly differential expression of the monocarboxylate transporters MCT2 and MCT4 in the developing rat brain. Neuroscience 2003; 122: 677-688
38. Broer S, Rahman B, Pellegri G, Pellerin L, Martin JL, Verleysdonk S, et al. Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT 1) expressing Xenopus laevis oocytes. Expression of two different monocarboxylate transporters in astroglial cells and neurons. J Biol Chem 1997; 272: 30096-30102
39. Debernardi R, Pierre K, Lengacher S, Magistretti PJ, Pellerin L. Cell-specific expression pattern of monocarboxylate transporters in astrocytes and neurons observed in different mouse brain cortical cell cultures. J Neurosci Res 2003; 73: 141-155
40. Gerhart DZ, Enerson BE, Zhdankina OY, Leino RL, Drewes LR. Expression of monocarboxylate transporter MCT1 by brain endothelium and glia in adult and suckling rats. Am J Physiol 1997; 273: E207-E213
41. 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
42. Bergersen LH. Lactate transport and signaling in the brain: potential therapeutic targets and roles in body-brain interaction. J Cereb Blood Flow Metab 2015; 35: 176-185
43. Nedergaard M, Goldman SA. Carrier-mediated transport of lactic acid in cultured neurons and astrocytes. Am J Physiol 1993; 265: R282-R289
44. Broer S, Schneider HP, Broer A, Rahman B, Hamprecht B, Deitmer JW. Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH. Biochem J 1998; 333: 167-174
45. 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
46. Herrero-Mendez A, Almeida A, Fernandez E, Maestre C, Moncada S, Bolanos JP. The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C-Cdh1. Nat Cell Biol 2009; 11: 747-752
47. Gibbs ME, Hertz L. Inhibition of astrocytic energy metabolism by D-lactate exposure impairs memory. Neurochem Int2008; 52: 1012-1018
48. Gibbs ME, Lloyd HG, Santa T, Hertz L. Glycogen is a preferred glutamate precursor during learning in 1-day-old chick: biochemical and behavioral evidence. J Neurosci Res 2007; 85: 3326-3333
49. Newman LA, Korol DL, Gold PE. Lactate produced by glycogenolysis in astrocytes regulates memory processing. PLoS One 2011; 6: e28427
50. Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, et al. Astrocyte-neuron lactate transport is required for long-Term memory formation. Cell 2011; 144: 810-823
51. Hanstock TL, Mallet PE, Clayton EH. Increased plasma d-lactic acid associated with impaired memory in rats. Physiol Behav 2010; 101: 653-659
52. Hall CN, Klein-Flugge MC, Howarth C, Attwell D. Oxidative phosphorylation, not glycolysis, powers presynaptic and postsynaptic mechanisms underlying brain information processing. J Neurosci 2012; 32: 8940-8951
53. DiNuzzo M, Mangia S, Maraviglia B, Giove F. Glycogenolysis in astrocytes supports blood-borne glucose channeling not glycogen-derived lactate shuttling to neurons: evidence from mathematical modeling. J Cereb Blood Flow Metab 2010; 30: 1895-1904
54. Lee DK, Nguyen T, Lynch KR, Cheng R, Vanti WB, Arkhitko O, et al. Discovery and mapping of ten novel G protein-coupled receptor genes. Gene 2001; 275: 83-91
55. Cai TQ, Ren N, Jin L, Cheng K, Kash S, Chen R, et al. Role of GPR81 in lactatemediated reduction of adipose lipolysis. Biochem Biophys Res Commun 2008; 377: 987-991
56. Liu C, Kuei C, Zhu J, Yu J, Zhang L, Shih A, et al. 3, 5-Dihydroxybenzoic acid, a specific agonist for hydroxycarboxylic acid 1, inhibits lipolysis in adipocytes. J Pharmacol Exp Ther 2012; 341: 794-801
57. Liu C, Wu J, Zhu J, Kuei C, Yu J, Shelton J, et al. Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81. J Biol Chem 2009; 284: 2811-2822
58. Lauritzen KH, Morland C, Puchades M, Holm-Hansen S, Hagelin EM, Lauritzen F, et al. Lactate receptor sites link neurotransmission, neurovascular coupling, and brain energy metabolism. Cereb Cortex 2013; 24: 2784-2795
59. Bozzo L, Puyal J, Chatton JY. Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway. PLoS ONE 2013; 8: e71721
60. Gilbert E, Tang JM, Ludvig N, Bergold PJ. Elevated lactate suppresses neuronal firing in vivo and inhibits glucose metabolism in hippocampal slice cultures. Brain Res 2006; 1117: 213-223
61. Tang F, Lane S, Korsak A, Paton JF, Gourine AV, Kasparov S, et al. Lactate-mediated glia-neuronal signalling in the mammalian brain. Nat Commun 2014; 5: 3284
62. Matsuo M, Kimura Y, Ueda K. KATP channel interaction with adenine nucleotides. J Mol Cell Cardiol 2005; 38: 907-916
63. Yokoshiki H, Sunagawa M, Seki T, Sperelakis N. ATP-sensitive K+ channels in pancreatic, cardiac, and vascular smooth muscle cells. Am J Physiol 1998; 274: C25-C37
64. Edwards G, Weston AH. The pharmacology of ATP-sensitive potassium channels. Annu Rev Pharmacol Toxicol 1993; 33: 597-637
65. Karschin C, Ecke C, Ashcroft FM, Karschin A. Overlapping distribution of K(ATP) channel-forming Kir6.2 subunit and the sulfonylurea receptor SUR1 in rodent brain. FEBS Lett 1997; 401: 59-64
66. Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW. Central nervous system control of food intake and body weight. Nature 2006; 443: 289-295
67. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G proteincoupled receptors that regulate feeding behavior. Cell 1998; 92: 573-585
68. Parsons MP, Hirasawa M. ATP-sensitive potassium channel-mediated lactate effect on orexin neurons: implications for brain energetics during arousal. J Neurosci 2010; 30: 8061-8070
69. Venner A, Karnani MM, Gonzalez JA, Jensen LT, Fugger L, Burdakov D. Orexin neurons as conditional glucosensors: paradoxical regulation of sugar sensing by intracellular fuels. J Physiol 2011; 589: 5701-5708
70. Kang L, Dunn-Meynell AA, Routh VH, Gaspers LD, Nagata Y, Nishimura T, et al. Glucokinase is a critical regulator of ventromedial hypothalamic neuronal glucosensing. Diabetes 2006; 55: 412-420
71. Ainscow EK, Mirshamsi S, Tang T, Ashford ML, Rutter GA. Dynamic imaging of free cytosolic ATP concentration during fuel sensing by rat hypothalamic neurones: evidence for ATP-independent control of ATP-sensitive K(+) channels. J Physiol 2002; 544: 429-445
72. Yang XJ, Kow LM, Funabashi T, Mobbs CV. Hypothalamic glucose sensor: similarities to and differences from pancreatic beta-cell mechanisms. Diabetes 1999; 48: 1763-1772
73. Yang J, Ruchti E, Petit JM, Jourdain P, Grenningloh G, Allaman I, et al. Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons. Proc Natl Acad Sci USA 2014; 111: 12228-12233
74. Kohr G, Eckardt S, Luddens H, Monyer H, Seeburg PH. NMDA receptor channels: subunit-specific potentiation by reducing agents. Neuron 1994; 12: 1031-1040
75. Sullivan JM, Traynelis SF, Chen HS, Escobar W, Heinemann SF, Lipton SA. Identification of two cysteine residues that are required for redox modulation of the NMDA subtype of glutamate receptor. Neuron 1994; 13: 929-936
76. Giffard RG, Monyer H, Christine CW, Choi DW. Acidosis reduces NMDA receptor activation, glutamate neurotoxicity, and oxygen-glucose deprivation neuronal injury in cortical cultures. Brain Res 1990; 506: 339-342
77. Tang CM, Dichter M, Morad M. Modulation of the N-methyl-D-Aspartate channel by extracellular H+. Proc Natl Acad Sci USA 1990; 87: 6445-6449
78. Ahmed K, Tunaru S, Offermanns S. GPR109A, GPR109B and GPR81, a family of hydroxy-carboxylic acid receptors. Trends Pharmacol Sci 2009; 30: 557-562
79. Bergersen LH, Gjedde A. Is lactate a volume transmitter of metabolic states of the brain? Front Neuroenergetics 2012; 4: 5
80. Barros LF, San Martin A, Sotelo-Hitschfeld T, Lerchundi R, Fernandez-Moncada I, Ruminot I, et al. Small is fast: astrocytic glucose and lactate metabolism at cellular resolution. Front Cell Neurosci 2013; 7: 27