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Cell Metab. 2016 Jan 12;23(1):94-102. doi: 10.1016/j.cmet.2015.10.010. Epub 2015 Nov 19.

In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons.

Author information

1
Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8092 Zurich, Switzerland.
2
Brain Mind Institute, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
3
Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Centro de Estudios Científicos, Valdivia 5110466, Chile.
4
Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland.
5
Centro de Estudios Científicos, Valdivia 5110466, Chile.
6
Brain Mind Institute, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland; Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.
7
Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8092 Zurich, Switzerland. Electronic address: bweber@pharma.uzh.ch.

Abstract

Investigating lactate dynamics in brain tissue is challenging, partly because in vivo data at cellular resolution are not available. We monitored lactate in cortical astrocytes and neurons of mice using the genetically encoded FRET sensor Laconic in combination with two-photon microscopy. An intravenous lactate injection rapidly increased the Laconic signal in both astrocytes and neurons, demonstrating high lactate permeability across tissue. The signal increase was significantly smaller in astrocytes, pointing to higher basal lactate levels in these cells, confirmed by a one-point calibration protocol. Trans-acceleration of the monocarboxylate transporter with pyruvate was able to reduce intracellular lactate in astrocytes but not in neurons. Collectively, these data provide in vivo evidence for a lactate gradient from astrocytes to neurons. This gradient is a prerequisite for a carrier-mediated lactate flux from astrocytes to neurons and thus supports the astrocyte-neuron lactate shuttle model, in which astrocyte-derived lactate acts as an energy substrate for neurons.

PMID:
26698914
DOI:
10.1016/j.cmet.2015.10.010
[Indexed for MEDLINE]
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