Cerebral glucose and lactate consumption during cerebral activation by physical activity in humans

FASEB Journal

Volumn 25, Issue 9, 2011, Pages 2865-2873

  Rasmussen, Peter ^a   Wyss, Matthias T ^a   Lundby, Carsten ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

Adrenaline; Blood flow; Energy metabolism; Exercise; Neuroenergetics; Transcranial ultrasound Doppler

Indexed keywords

ADRENALIN; GLUCOSE; LACTIC ACID; PROPRANOLOL;

ADRENERGIC SYSTEM; ARTERIAL BLOOD; BRAIN BLOOD FLOW; BRAIN GLUCOSE CONSUMPTION; BRAIN LACTATE CONSUMPTION; BRAIN METABOLISM; BRAIN OXYGEN CONSUMPTION; CARBOHYDRATE METABOLISM; CENTRAL NERVOUS SYSTEM FUNCTION; CEREBRAL METABOLIC RATE OF GLUCOSE; CEREBRAL METABOLIC RATE OF LACTATE; CEREBRAL METABOLIC RATE OF OXYGEN; EXERCISE; EXERCISE INTENSITY; GLUCOSE BLOOD LEVEL; GLUCOSE BRAIN LEVEL; HUMAN; LACTATE BLOOD LEVEL; META ANALYSIS; METABOLIC RATE; NERVOUS SYSTEM PARAMETERS; PHYSICAL ACTIVITY; PRIORITY JOURNAL; REST; REVIEW; SYSTEMATIC REVIEW;

BLOOD GLUCOSE; CEREBRUM; EXERCISE; GLUCOSE; HUMANS; LACTIC ACID; OXIDATION-REDUCTION;

EID: 80052689581     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.11-183822     Document Type: Review

References (73)

1. Olesen, J. (1971) Contralateral focal increase of cerebral blood flow in man during arm work. Brain 94, 646-653
2. Fox, P. T., and Raichle, M. E. (1986) Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc. Natl. Acad. Sci. U. S. A. 83, 1140-1144
3. Fox, P. T., Raichle, M. E., Mintun, M. A., and Dence, C. (1988) Nonoxidative glucose consumption during focal physiologic neural activity. Science 241, 462-464
4. Ide, K., Horn, A., and Secher, N. (1999) Cerebral metabolic response to submaximal exercise. J. Appl. Physiol. 87, 1604-1608
5. Volianitis, S., Fabricius-Bjerre, A., Overgaard, A., Stromstad, M., Bjarrum, M., Carlsson, C., Petersen, N., Rasmussen, P., Secher, N. H., and Nielsen, H. B. (2008) The cerebral metabolic ratio is not affected by oxygen availability during maximal exercise in humans. J. Physiol. 586, 107-112
6. Carlsson, C., Hagerdal, M., Kaasik, A. E., and Siesjo, B. K. (1977) A catecholamine-mediated increase in cerebral oxygen uptake during immobilisation stress in rats. Brain Res. 119, 223-231
7. Schmalbruch, I. K., Linde, R., Paulson, O. B., and Madsen, P. L. (2002) Activation-induced resetting of cerebral metabolism and flow is abolished by beta-adrenergic blockade with propranolol. Stroke 33, 251-255
8. Larsen, T. S., Rasmussen, P., Overgaard, M., Secher, N. H., and Nielsen, H. B. (2008) Non-selective beta-adrenergic blockade prevents reduction of the cerebral metabolic ratio during exhaustive exercise in humans. J. Physiol. 586, 2807-2815
9. Seifert, T. S., Brassard, P., Jorgensen, T. B., Hamada, A. J., Rasmussen, P., Quistorff, B., Secher, N. H., and Nielsen, H. B. (2009) Cerebral non-oxidative carbohydrate consumption in humans driven by adrenaline. J. Physiol. 587, 285-293
10. Quistorff, B., Secher, N. H., and Van Lieshout, J. J. (2008) Lactate fuels the human brain during exercise. FASEB J. 22, 3443-3449
11. Boumezbeur, F., Petersen, K. F., Cline, G. W., Mason, G. F., Behar, K. L., Shulman, G. I., and Rothman, D. L. (2010) The contribution of blood lactate to brain energy metabolism in humans measured by dynamic 13C nuclear magnetic resonance spectroscopy. J. Neurosci. 30, 13983-13991
12. Hasselbalch, S., Knudsen, G., Jakobsen, J., Hageman, L., Holm, S., and Paulson, O. B. (1994) Brain metabolism during shortterm starvation in humans. J. Cereb. Blood Flow Metab. 14, 125-131
13. Dalsgaard, M. K., Ide, K., Cai, Y., Quistorff, B., and Secher, N. H. (2002) The intent to exercise influences the cerebral O(2)/carbohydrate uptake ratio in humans. J. Physiol. 540, 681-689
14. Rasmussen, P., Plomgaard, P., Krogh-Madsen, R., Kim, Y. S., van Lieshout, J. J., Secher, N. H., and Quistorff, B. (2006) MCA Vmean and the arterial lactate-to-pyruvate ratio correlate during rhythmic handgrip. J. Appl. Physiol. 101, 1406-1411
15. Rasmussen, P., Madsen, C. A., Nielsen, H. B., Zaar, M., Gjedde, A., Secher, N. H., and Quistorff, B. (2009) Coupling between the blood lactate-to-pyruvate ratio and MCA Vmean at the onset of exercise in humans. J. Appl. Physiol. 107, 1799-1805
16. Rasmussen, P., Nyberg, N., Jaroszewski, J. W., Krogh-Madsen, R., Secher, N. H., and Quistorff, B. (2010) Brain nonoxidative carbohydrate consumption is not explained by export of an unknown carbon source: evaluation of the arterial and jugular venous metabolome. J. Cereb. Blood Flow Metab. 30, 1240-1246
17. Rasmussen, P., Overgaard, A., Fabricius-Bjerre, A., Bjarrum, M., Carlsson, C., Petersen, N., Nielsen, H. B., Volianitis, S., Gjedde, A., and Secher, N. H. (2010) The effects of normoxia, hypoxia, and hyperoxia on cerebral haemoglobin saturation using near infrared spectroscopy during maximal exercise. Int. J. Ind. Ergon. 40, 190-196
18. Seifert, T., Rasmussen, P., Secher, N. H., and Nielsen, H. B. (2009) Cerebral oxygenation decreases during exercise in humans with beta-adrenergic blockade. Acta Physiol. (Oxf.) 196, 295-302
19. van Hall, G., Stromstad, M., Rasmussen, P., Jans, O., Zaar, M., Gam, C., Quistorff, B., Secher, N. H., and Nielsen, H. B. (2009) Blood lactate is an important energy source for the human brain. J. Cereb. Blood Flow Metab. 29, 1121-1129
20. Smith, D., Pernet, A., Hallett, W. A., Bingham, E., Marsden, P. K., and Amiel, S. A. (2003) Lactate: a preferred fuel for human brain metabolism in vivo. J. Cereb. Blood Flow Metab. 23, 658-664
21. Kemppainen, J., Aalto, S., Fujimoto, T., Kalliokoski, K. K., Langsjo, J., Oikonen, V., Rinne, J., Nuutila, P., and Knuuti, J. (2005) High intensity exercise decreases global brain glucose uptake in humans. J. Physiol. 568, 323-332
22. Dalsgaard, M. K., Quistorff, B., Danielsen, E. R., Selmer, C., Vogelsang, T., and Secher, N. H. (2004) A reduced cerebral metabolic ratio in exercise reflects metabolism and not accumulation of lactate within the human brain. J. Physiol. 554, 571-578
23. Gam, C. M., Rasmussen, P., Secher, N. H., Seifert, T., Larsen, F. S., and Nielsen, H. B. (2009) Maintained cerebral metabolic ratio during exercise in patients with beta-adrenergic blockade. Clin. Physiol. Funct. Imaging 29, 420-426
24. Seifert, T., Rasmussen, P., Brassard, P., Homann, P. H., Wissenberg, M., Nordby, P., Stallknecht, B., Secher, N. H., and Nielsen, H. B. (2009) Cerebral oxygenation and metabolism during exercise following three months of endurance training in healthy overweight males. Am. J. Physiol. 297, R867-876
25. 2 uptake in human brain during recovery from maximal exercise. J. Physiol. 522, 159-164
26. Serrador, J. M., Picot, P. A., Rutt, B. K., Shoemaker, J. K., and Bondar, R. L. (2000) MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis. Stroke 31, 1672-1678
27. Giller, C. A., Bowman, G., Dyer, H., Mootz, L., Krippner, W., Loftus, C. M., and Muizelaar, J. P. (1993) Cerebral arterial diameters during changes in blood-pressure and carbon-dioxide during craniotomy. Neurosurgery 32, 737-742
28. Jørgensen, L. G. (1995) Transcranial Doppler ultrasound for cerebral perfusion. Acta Physiol. Scand. Suppl. 625, 1-44
29. 2 reactivity during strenuous exercise in man. Eur. J. Appl. Physiol. 96, 299-304
30. Madsen, P. L., Holm, S., Herning, M., and Lassen, N. A. (1993) Average blood flow and oxygen uptake in the human brain during resting wakefulness: a critical appraisal of the Kety-Schmidt technique. J. Cereb. Blood Flow Metab. 13, 646-655
31. Rasmussen, P., Dawson, E. A., Nybo, L., van Lieshout, J. J., Secher, N. H., and Gjedde, A. (2007) Capillary-oxygenation-level-dependent near-infrared spectrometry in frontal lobe of humans. J. Cereb. Blood Flow Metab. 27, 1082-1093
32. LaManna, J. C., and Harik, S. I. (1985) Regional comparisons of brain glucose influx. Brain Res. 326, 299-305
33. Delp, M., Armstrong, R., Godfrey, D., Laughlin, M., Ross, C., and Wilkerson, M. (2001) Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine. J. Physiol. 533, 849-859
34. Fukuyama, H., Ouchi, Y., Matsuzaki, S., Nagahama, Y., Yamauchi, H., Ogawa, M., Kimura, J., and Shibasaki, H. (1997) Brain functional activity during gait in normal subjects: a SPECT study. Neurosci. Lett. 228, 183-186
35. Vlassenko, A. G., Rundle, M. M., and Mintun, M. A. (2006) Human brain glucose metabolism may evolve during activation: findings from a modified FDG PET paradigm. Neuroimage 33, 1036-1041
36. Nybo, L., and Rasmussen, P. (2007) Inadequate cerebral oxygen delivery and central fatigue during strenuous exercise. Exerc. Sport Sci. Rev. 35, 110-118
37. Pott, F., Jensen, K., Hansen, H., Christensen, N. J., Lassen, N. A., and Secher, N. H. (1996) Middle cerebral artery blood velocity and plasma catecholamines during exercise. Acta Physiol. Scand. 158, 349-356
38. Berntman, L., Dahlgren, N., and Siesjo, B. K. (1978) Influence of intravenously administered catecholamines on cerebral oxygen consumption and blood flow in the rat. Acta Physiol. Scand. 104, 101-108
39. Hemmingsen, R., Hertz, M. M., and Barry, D. I. (1979) The effect of propranolol on cerebral oxygen consumption and blood flow in the rat: measurements during normocapnia and hypercapnia. Acta Physiol. Scand. 105, 274-281
40. Nybo, L., Nielsen, B., Blomstrand, E., Moller, K., and Secher, N. (2003) Neurohumoral responses during prolonged exercise in humans. J. Appl. Physiol. 95, 1125-1131
41. Richter, E. A., Ruderman, N. B., Gavras, H., Belur, E. R., and Galbo, H. (1982) Muscle glycogenolysis during exercise: dual control by epinephrine and contractions. Am. J. Physiol. 242, E25-32
42. Madsen, P. L., Cruz, N. F., and Dienel, G. A. (1995) Metabolic flux to and from brain and levels of metabolites in brain of rats during rest, sensory stimulation, and recovery. J. Cereb. Blood Flow Metab. 15, S77
43. Madsen, P. L., Hasselbalch, S. G., Hagemann, L. P., Olsen, K. S., Bülow, J., Holm, S., Wildschiødtc, G., Paulson, O. B., and Lassen, N. A. (1995) Persistent resetting of the cerebral oxygen/glucose uptake by brain activation: evidence obtained with the Kety-Schmidt technique. J. Cereb. Blood Flow Metab. 15, 485-491
44. Caesar, K., Hashemi, P., Douhou, A., Bonvento, G., Boutelle, M. G., Walls, A. B., and Lauritzen, M. (2008) Glutamate receptor-dependent increments in lactate, glucose and oxygen metabolism evoked in rat cerebellum in vivo. J. Physiol. 586, 1337-1349
45. Zielke, H. R., Zielke, C. L., Baab, P. J., and Tildon, J. T. (2007) Effect of fluorocitrate on cerebral oxidation of lactate and glucose in freely moving rats. J. Neurochem. 101, 9-16
46. Rasmussen, P., Nielsen, J., Overgaard, M., Krogh-Madsen, R., Gjedde, A., Secher, N. H., and Petersen, N. C. (2010) Reduced muscle activation during exercise related to brain oxygenation and metabolism in humans. J. Physiol. 588, 1985-1995
47. Juel, C., and Halestrap, A. P. (1999) Lactate transport in skeletal muscle - role and regulation of the monocarboxylate transporter. J. Physiol. 517(Pt. 3), 633-642
48. Dalsgaard, M. K. (2006) Fuelling cerebral activity in exercising man. J. Cereb. Blood Flow Metab. 26, 731-750
49. Chih, C.-P., Lipton, P., and Roberts, E. L. (2001) Do active cerebral neurons really use lactate rather than glucose? Trends Neurosci. 24, 573-578
50. Madsen, P. L., Schmidt, J. F., Holm, S., Jørgensen, H., Wildschiødtc, G., Christensen, N. J., Friberg, L., Vorstrup, S., and Lassen, N. A. (1992) Mental stress and cognitive performance do not increase overall level of cerebral O2 uptake in humans. J. Appl. Physiol. 73, 420-426
51. Schmoll, D., Führmann, E., Gebhardt, R., and Hamprecht, B. (1995) Significant amounts of glycogen are synthesized from 3-carbon compounds in astroglial primary cultures from mice with participation of the mitochondrial phosphoenolpyruvate carboxykinase isoenzyme. Eur. J. Biochem. 227, 308-315
52. Wiesinger, H., Hamprecht, B., and Dringen, R. (1997) Metabolic pathways for glucose in astrocytes. Glia 21, 22-34
53. DiNuzzo, M., Mangia, S., Maraviglia, B., and Giove, F. (2010) Glycogenolysis in astrocytes supports blood-borne glucose channeling not glycogen-derived lactate shuttling to neurons: evidence from mathematical modeling. J. Cereb. Blood Flow Metab. 30, 1895-1904
54. Rasmussen, P., Vedel, J. C., Olesen, J., Adser, H., Pedersen, M. V., Hart, E., Secher, N. H., and Pilegaard, H. (2011) In humans IL-6 is released from the brain during and after exercise and paralleled by enhanced IL-6 mRNA expression in the hippocampus of mice. Acta Physiol. (Oxf.) 201, 475-482
55. Ball, K. K., Cruz, N. F., Mrak, R. E., and Dienel, G. A. (2010) Trafficking of glucose, lactate, and amyloid-beta from the inferior colliculus through perivascular routes. J. Cereb. Blood Flow Metab. 30, 162-176
56. Nybo, L., Dalsgaard, M. K., Steensberg, A., Moller, K., and Secher, N. H. (2005) Cerebral ammonia uptake and accumulation during prolonged exercise in humans. J. Physiol. 563, 285-290
57. Nybo, L., Nielsen, B., Pedersen, B. K., Moller, K., and Secher, N. H. (2002) Interleukin-6 release from the human brain during prolonged exercise. J. Physiol. 542, 991-995
58. Nybo, L., Moller, K., Pedersen, B. K., Nielsen, B., and Secher, N. H. (2003) Association between fatigue and failure to preserve cerebral energy turnover during prolonged exercise. Acta Physiol. Scand. 179, 67-74
59. Rasmussen, P., Brassard, P., Adser, H., Pedersen, M. V., Leick, L., Hart, E., Secher, N. H., Pedersen, B. K., and Pilegaard, H. (2009) Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp. Physiol. 94, 1062-1069
60. Seifert, T., Brassard, P., Wissenberg, M., Rasmussen, P., Nordby, P., Stallknecht, B., Adser, H., Jakobsen, A. H., Pilegaard, H., Nielsen, H. B., and Secher, N. H. (2010) Endurance training enhances BDNF release from the human brain. Am. J. Physiol. 298, R372-R377
61. Lossner, B., Jork, R., Lindner, M., Lucke, B., and Matthies, H. (1984) Dopamine stimulated glycosylation of brain proteins in vitro is inhibited only partially by dopamine receptor antagonists. Biomed. Biochim. Acta 43, 775-787
62. Hoffmann, A., Nimtz, M., Wurster, U., and Conradt, H. S. (1994) Carbohydrate structures of beta-trace protein from human cerebrospinal fluid: evidence for "brain-type" N-glycosylation. J. Neurochem. 63, 2185-2196
63. Khidekel, N., Ficarro, S. B., Peters, E. C., and Hsieh-Wilson, L. C. (2004) Exploring the O-GlcNAc proteome: direct identification of O-GlcNAc-modified proteins from the brain. Proc. Natl. Acad. Sci. U. S. A. 101, 13132-13137
64. Attwell, D., Buchan, A. M., Charpak, S., Lauritzen, M., Macvicar, B. A., and Newman, E. A. (2010) Glial and neuronal control of brain blood flow. Nature 468, 232-243
65. Gordon, G. R., Choi, H. B., Rungta, R. L., Ellis-Davies, G. C., and MacVicar, B. A. (2008) Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature 456, 745-749
66. Ido, Y., Chang, K., and Williamson, J. R. (2004) NADH augments blood flow in physiologically activated retina and visual cortex. Proc. Natl. Acad. Sci. U. S. A. 101, 653-658
67. Ido, Y., Chang, K., Woolsey, T. A., and Williamson, J. R. (2001) NADH: sensor of blood flow need in brain, muscle, and other tissues. FASEB J. 15, 1419-1421
68. Mintun, M. A., Vlassenko, A. G., Rundle, M. M., and Raichle, M. E. (2004) Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain. Proc. Natl. Acad. Sci. U. S. A. 101, 659-664
69. Vlassenko, A. G., Rundle, M. M., Raichle, M. E., and Mintun, M. A. (2006) Regulation of blood flow in activated human brain by cytosolic NADH/NAD+ ratio. Proc. Natl. Acad. Sci. U. S. A. 103, 1964-1969
70. Blomqvist, G., Gjedde, A., Gutniak, M., Grill, V., Widen, L., Stone-Elander, S., and Hellstrand, E. (1991) Facilitated transport of glucose from blood to brain in man and the effect of moderate hypoglycaemia on cerebral glucose utilization. Eur. J. Nucl. Med. 18, 834-837
71. Magistretti, P. J., and Pellerin, L. (1999) Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos. Trans. R. Soc. Lond. B Biol. Sci. 354, 1155-1163
72. Dager, S. R., Friedman, S. D., Heide, A., Layton, M. E., Richards, T., Artru, A., Strauss, W., Hayes, C., and Posse, S. (1999) Two-dimensional proton echo-planar spectroscopic imaging of brain metabolic changes during lactate-induced panic. Arch. Gen. Psychiatry 56, 70-77
73. Lin, A.-L., Fox, P. T., Hardies, J., Duong, T. Q., and Gao, J.-H. (2010) Nonlinear coupling between cerebral blood flow, oxygen consumption, and ATP production in human visual cortex. Proc. Natl. Acad. Sci. U. S. A. 107, 8446-8451