Brain lactate kinetics: Modeling evidence for neuronal lactate uptake upon activation.

Details

Serval ID
serval:BIB_C04195B31BC9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Brain lactate kinetics: Modeling evidence for neuronal lactate uptake upon activation.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Aubert A., Costalat R., Magistretti P.J., Pellerin L.
ISSN
0027-8424
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
102
Number
45
Pages
16448-53
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
A critical issue in brain energy metabolism is whether lactate produced within the brain by astrocytes is taken up and metabolized by neurons upon activation. Although there is ample evidence that neurons can efficiently use lactate as an energy substrate, at least in vitro, few experimental data exist to indicate that it is indeed the case in vivo. To address this question, we used a modeling approach to determine which mechanisms are necessary to explain typical brain lactate kinetics observed upon activation. On the basis of a previously validated model that takes into account the compartmentalization of energy metabolism, we developed a mathematical model of brain lactate kinetics, which was applied to published data describing the changes in extracellular lactate levels upon activation. Results show that the initial dip in the extracellular lactate concentration observed at the onset of stimulation can only be satisfactorily explained by a rapid uptake within an intraparenchymal cellular compartment. In contrast, neither blood flow increase, nor extracellular pH variation can be major causes of the lactate initial dip, whereas tissue lactate diffusion only tends to reduce its amplitude. The kinetic properties of monocarboxylate transporter isoforms strongly suggest that neurons represent the most likely compartment for activation-induced lactate uptake and that neuronal lactate utilization occurring early after activation onset is responsible for the initial dip in brain lactate levels observed in both animals and humans.
Keywords
Animals, Brain, Energy Metabolism, Humans, Hydrogen-Ion Concentration, Lactic Acid, Mathematics, Models, Biological, Monocarboxylic Acid Transporters, NAD, Neurons
Pubmed
Web of science
Open Access
Yes
Create date
05/02/2008 13:38
Last modification date
20/08/2019 15:34
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