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research article

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

Aubert, Agnès
•
Costalat, Robert
•
Magistretti, Pierre J  
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2005
Proceedings Of The National Academy Of Sciences Of The United States Of America (PNAS)

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.

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Type
research article
DOI
10.1073/pnas.0505427102
Web of Science ID

WOS:000233283700058

PubMed ID

16260743

Author(s)
Aubert, Agnès
Costalat, Robert
Magistretti, Pierre J  
Pellerin, Luc
Date Issued

2005

Publisher

National Academy of Sciences

Published in
Proceedings Of The National Academy Of Sciences Of The United States Of America (PNAS)
Volume

102

Issue

45

Start page

16448

End page

53

Subjects

Energy Metabolism

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LNDC  
Available on Infoscience
January 8, 2010
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/45194
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