title: In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons.
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.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8092 Zurich, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Mächler
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8092 Zurich, Switzerland.
authors.forename: Matthias T
authors.initials: MT
authors.lastname: Wyss
authors.affiliation: Brain Mind Institute, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Maha
authors.initials: M
authors.lastname: Elsayed
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8092 Zurich, Switzerland.
authors.forename: Jillian
authors.initials: J
authors.lastname: Stobart
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Centro de Estudios Científicos, Valdivia 5110466, Chile.
authors.forename: Robin
authors.initials: R
authors.lastname: Gutierrez
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: von Faber-Castell
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Vincens
authors.initials: V
authors.lastname: Kaelin
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8092 Zurich, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Zuend
authors.affiliation: Centro de Estudios Científicos, Valdivia 5110466, Chile.
authors.forename: Alejandro
authors.initials: A
authors.lastname: San Martín
authors.affiliation: Centro de Estudios Científicos, Valdivia 5110466, Chile.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Romero-Gómez
authors.affiliation: Centro de Estudios Científicos, Valdivia 5110466, Chile.
authors.forename: Felipe
authors.initials: F
authors.lastname: Baeza-Lehnert
authors.affiliation: Brain Mind Institute, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lengacher
authors.affiliation: Brain Mind Institute, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Schneider
authors.affiliation: Brain Mind Institute, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Aebischer
authors.affiliation: 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.
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Magistretti
authors.affiliation: Centro de Estudios Científicos, Valdivia 5110466, Chile.
authors.forename: L Felipe
authors.initials: LF
authors.lastname: Barros
authors.affiliation: 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.
authors.forename: Bruno
authors.initials: B
authors.lastname: Weber
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D019344:Lactic Acid / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism*
chemical_list: D019344:Lactic Acid