In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons

Philipp Mächler, Matthias T. Wyss, Maha Elsayed, Jillian Stobart, Robin Gutierrez, Alexandra von Faber-Castell, Vincens Kaelin, Marc Zuend, Alejandro San Martín, Ignacio Romero-Gómez, Felipe Baeza-Lehnert, Sylvain Lengacher, Bernard L. Schneider, Patrick Aebischer, Pierre J. Magistretti, L. Felipe Barros, Bruno Weber

Research output: Contribution to journalArticlepeer-review

260 Scopus citations

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. © 2016 Elsevier Inc.
Original languageEnglish (US)
Pages (from-to)94-102
Number of pages9
JournalCell Metabolism
Volume23
Issue number1
DOIs
StatePublished - Nov 19 2015

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