Astrocytes are poised for lactate trafficking and release from activated brain and for supply of glucose to neurons.
Brain is a highly-oxidative organ, but during activation, glycolytic flux is preferentially up-regulated even though oxygen supply is adequate. The biochemical and cellular basis of metabolic changes during brain activation and the fate of lactate produced within brain are important, unresolved issues central to understanding brain function, brain images, and spectroscopic data. Because in vivo brain imaging studies reveal rapid efflux of labeled glucose metabolites during activation, lactate trafficking among astrocytes and between astrocytes and neurons was examined after devising specific, real-time, sensitive enzymatic fluorescent assays to measure lactate and glucose levels in single cells in adult rat brain slices. Astrocytes have a 2- to 4-fold faster and higher capacity for lactate uptake from extracellular fluid and for lactate dispersal via the astrocytic syncytium compared to neuronal lactate uptake from extracellular fluid or shuttling of lactate to neurons from neighboring astrocytes. Astrocytes can also supply glucose to neurons as well as glucose can be taken up by neurons from extracellular fluid. Astrocytic networks can provide neuronal fuel and quickly remove lactate from activated glycolytic domains, and the lactate can be dispersed widely throughout the syncytium to endfeet along the vasculature for release to blood or other brain regions via perivascular fluid flow.
Gandhi
Gautam K
GK
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Cruz
Nancy F
NF
Ball
Kelly K
KK
Dienel
Gerald A
GA
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D005453:Fluorescence; D017629:Gap Junctions / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007245:Inferior Colliculi / Q000166:cytology / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar
D019344:Lactic Acid; D005947:Glucose
Dev Neurosci. 1998;20(4-5):300-9
9778566
J Neurosci Res. 2001 Dec 1;66(5):747-54
11746398
J Cereb Blood Flow Metab. 2003 Nov;23(11):1263-81
14600433
J Neurosci. 2008 May 7;28(19):4888-96
18463242
J Cereb Blood Flow Metab. 1989 Dec;9(6):911-3
2584281
Trends Neurosci. 1996 Aug;19(8):319-25
8843600
Cellscience. 2009 Jan 27;5(3):34-43
19756252
J Cereb Blood Flow Metab. 2007 Feb;27(2):219-49
16835632
J Physiol. 2008 Mar 1;586(5):1337-49
18187464
J Neurosci Methods. 1998 Dec 31;86(1):35-54
9894784
Glia. 1996 Mar;16(3):187-95
8833189
J Neurochem. 2009 May;109 Suppl 1:87-93
19393013
J Cereb Blood Flow Metab. 2006 Jan;26(1):142-52
15973352
J Cereb Blood Flow Metab. 2006 Dec;26(12):1584-6
16639423
Glia. 2009 Jul;57(9):962-70
19062182
J Cereb Blood Flow Metab. 1982 Dec;2(4):394-407
6754750
Neurochem Int. 2006 May-Jun;48(6-7):586-95
16513214
J Neurosci Res. 2007 Nov 15;85(15):3244-53
17600826
J Cereb Blood Flow Metab. 2005 Nov;25(11):1476-90
15931164
Am J Physiol Endocrinol Metab. 2003 Nov;285(5):E1127-34
14534079
J Cereb Blood Flow Metab. 1988 Apr;8(2):193-200
3343294
J Neurochem. 2009 May;109 Suppl 1:30-7
19393006
J Cereb Blood Flow Metab. 1999 Apr;19(4):380-92
10197508
J Cereb Blood Flow Metab. 2007 Nov;27(11):1766-91
17579656
Anal Biochem. 1997 Nov 15;253(2):162-8
9367498
J Neurosci Res. 2007 Nov 15;85(15):3254-66
17265468
J Physiol. 2000 Dec 1;529 Pt 2:285-93
11101640
Eur J Biochem. 1986 Jul 1;158(1):159-65
2874024
J Cereb Blood Flow Metab. 1995 Jan;15(1):97-110
7798343
J Neurochem. 1977 May;28(5):897-916
864466
J Cereb Blood Flow Metab. 2009 Jun;29(6):1121-9
19337275
Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4188-93
17360498
Biochem J. 1975 Apr;148(1):97-106
1171687
Glia. 2007 Sep;55(12):1251-62
17659524
J Neurochem. 1987 Nov;49(5):1564-70
3668540
J Neurochem. 2009 May;109 Suppl 1:24-9
19393005
J Biol Chem. 2009 Mar 13;284(11):7091-9
19129175
Neurochem Int. 2004 Jul-Aug;45(2-3):321-51
15145548
Neuroscience. 2007 Mar 2;145(1):11-9
17218064
Nature. 2008 Dec 11;456(7223):745-9
18971930
Neurochem Int. 2006 May-Jun;48(6-7):523-30
16530294
J Neurochem. 1990 Aug;55(2):698-707
2164576
J Neurochem. 2009 May;109 Suppl 1:237-45
19393033
J Neurosci Res. 2001 Dec 1;66(5):824-38
11746408
J Neurochem. 2009 Aug;110(3):857-69
19457076
J Neurosci Res. 2007 Nov 15;85(15):3267-83
17600824
J Neurosci. 2002 Jan 1;22(1):183-92
11756501
Neurochem Int. 2003 Sep-Oct;43(4-5):339-54
12742078
Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10625-9
7938003
J Cereb Blood Flow Metab. 2006 Jul;26(7):865-77
16407855
Science. 2008 Dec 5;322(5907):1551-5
19056987
J Neurochem. 2009 May;109 Suppl 1:55-62
19393009
J Cereb Blood Flow Metab. 1987 Apr;7(2):154-60
3558498
Am J Physiol Heart Circ Physiol. 2006 Mar;290(3):H925-34
16299264
Radiology. 1990 Feb;174(2):328-30
2153309
Biochem J. 1975 Apr;148(1):85-96
1156402
J Cereb Blood Flow Metab. 2009 Mar;29(3):441-63
19002199
Brain Res. 1985 Feb 4;326(1):47-63
3971148
J Neurochem. 2006 Nov;99(4):1049-61
16899068
J Cereb Blood Flow Metab. 1989 Dec;9(6):774-85
2584274
Neurochem Int. 2004 Sep;45(4):467-77
15186912
Brain Res. 1990 Dec 24;537(1-2):333-6
2085783
Biochem J. 1974 Feb;138(2):313-6
4822737
Ann N Y Acad Sci. 2008 Dec;1147:139-70
19076439