title: In vivo evidence for lactate as a neuronal energy source.
abstract: Cerebral energy metabolism is a highly compartmentalized and complex process in which transcellular trafficking of metabolites plays a pivotal role. Over the past decade, a role for lactate in fueling the energetic requirements of neurons has emerged. Furthermore, a neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported. The majority of the current evidence concerning lactate metabolism at the cellular level is based on in vitro data; only a few recent in vivo results have demonstrated that the brain preferentially utilizes lactate over glucose. Using voltage-sensitive dye (VSD) imaging, beta-probe measurements of radiotracer kinetics, and brain activation by sensory stimulation in the anesthetized rat, we investigated several aspects of cerebral lactate metabolism. The present study is the first in vivo demonstration of the maintenance of neuronal activity in the presence of lactate as the primary energy source. The loss of the voltage-sensitive dye signal found during severe insulin-induced hypoglycemia is completely prevented by lactate infusion. Thus, lactate has a direct neuroprotective effect. Furthermore, we demonstrate that the brain readily oxidizes lactate in an activity-dependent manner. The washout of 1-[(11)C]L-lactate, reflecting cerebral lactate oxidation, was observed to increase during brain activation from 0.077 ± 0.009 to 0.105 ± 0.007 min(-1). Finally, our data confirm that the brain prefers lactate over glucose as an energy substrate when both substrates are available. Using [(18)F]fluorodeoxyglucose (FDG) to measure the local cerebral metabolic rate of glucose, we demonstrated a lactate concentration-dependent reduction of cerebral glucose utilization during experimentally increased plasma lactate levels.
authors: Institute of Pharmacology and Toxicology, University of Zürich, 8091 Zürich, Switzerland.
authors: Matthias T
authors: MT
authors: Wyss
authors: Renaud
authors: R
authors: Jolivet
authors: Alfred
authors: A
authors: Buck
authors: Pierre J
authors: PJ
authors: Magistretti
authors: Bruno
authors: B
authors: Weber
references: Brain Res. 2001 Mar 23;895(1-2):268-72
references: 11259789
references: J Neurophysiol. 2007 Jul;98(1):502-12
references: 17493915
references: Neuron. 2007 Apr 5;54(1):59-72
references: 17408578
references: J Neurosci. 2008 May 7;28(19):4888-96
references: 18463242
references: J Cereb Blood Flow Metab. 1991 Jul;11(4):581-6
references: 2050746
references: Nature. 2008 Dec 11;456(7223):745-9
references: 18971930
references: Neuroimage. 2009 Nov 1;48(2):339-47
references: 19591950
references: J Cereb Blood Flow Metab. 1981;1(2):155-85
references: 6276420
references: J Neurosci. 2010 Oct 20;30(42):13983-91
references: 20962220
references: Clin Sci (Lond). 1998 Feb;94(2):157-63
references: 9536924
references: J Cereb Blood Flow Metab. 1982 Dec;2(4):394-407
references: 6754750
references: J Cereb Blood Flow Metab. 2000 Feb;20(2):327-36
references: 10698070
references: J Cereb Blood Flow Metab. 2009 Nov;29(11):1780-9
references: 19675565
references: J Neurosci. 2004 Oct 27;24(43):9669-73
references: 15509754
references: Eur J Nucl Med Mol Imaging. 2002 Mar;29(3):319-23
references: 12002705
references: J Neurosci Res. 2005 Jan 1-15;79(1-2):11-8
references: 15586354
references: J Neurochem. 1977 May;28(5):897-916
references: 864466
references: J Cereb Blood Flow Metab. 2009 Jun;29(6):1121-9
references: 19337275
references: J Neurochem. 1997 Oct;69(4):1484-90
references: 9326277
references: Science. 1999 Jan 22;283(5401):496-7
references: 9988650
references: Lancet. 1994 Jan 1;343(8888):16-20
references: 7905041
references: Med Inform (Lond). 1998 Jul-Sep;23(3):207-14
references: 9785322
references: J Neurochem. 2000 Aug;75(2):480-6
references: 10899922
references: Am J Physiol. 1975 Nov;229(5):1165-9
references: 1200135
references: Science. 1985 Jul 5;229(4708):60-2
references: 2990038
references: J Cereb Blood Flow Metab. 2003 Dec;23(12):1455-60
references: 14663341
references: Am J Physiol. 1959 Dec;197:1205-10
references: 14437359
references: Brain. 2009 Oct;132(Pt 10):2839-49
references: 19700417
references: Eur J Neurosci. 2009 May;29(10):1951-63
references: 19453627
references: J Neurochem. 2009 Jul;110(2):423-40
references: 19457103
references: Eur Neuropsychopharmacol. 2002 Dec;12(6):495-501
references: 12468012
references: J Exp Biol. 2006 Jun;209(Pt 12):2304-11
references: 16731806
references: Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10625-9
references: 7938003
references: J Cereb Blood Flow Metab. 2006 Jul;26(7):865-77
references: 16407855
references: Science. 2008 Dec 5;322(5907):1551-5
references: 19056987
references: J Neurosci. 2004 Dec 15;24(50):11273-9
references: 15601933
references: Science. 1988 Jun 3;240(4857):1326-8
references: 3375817
references: Science. 2004 Jul 2;305(5680):99-103
references: 15232110
references: Neurochem Res. 1989 Jul;14(7):667-75
references: 2779727
references: Glia. 2007 Sep;55(12):1263-71
references: 17659525
references: Nat Cell Biol. 2009 Jun;11(6):747-52
references: 19448625
references: J Neurosci. 2010 Nov 10;30(45):15298-303
references: 21068334
references: Proc Nutr Soc. 1999 Nov;58(4):979-86
references: 10817166
references: J Physiol. 2008 Mar 1;586(5):1337-49
references: 18187464
references: Science. 2005 Aug 5;309(5736):943-7
references: 16081739
references: J Trauma. 1994 Dec;37(6):899-908
references: 7996602
references: Diabetes. 2006 Apr;55(4):929-34
references: 16567513
references: Prog Neurobiol. 1993 Feb;40(2):163-221
references: 8430212
references: Brain Res Rev. 2010 May;63(1-2):149-59
references: 19879896
references: Acta Physiol Scand. 1963 Aug;58:292-305
references: 14078649
references: J Cereb Blood Flow Metab. 2003 Nov;23(11):1282-6
references: 14600434
references: J Neurosci. 2010 Jun 16;30(24):8061-70
references: 20554857