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

doi:10.1016/j.cmet.2015.10.010

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

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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 language	English (US)
Pages (from-to)	94-102
Number of pages	9
Journal	Cell Metabolism
Volume	23
Issue number	1
DOIs	https://doi.org/10.1016/j.cmet.2015.10.010
State	Published - Nov 19 2015

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: This research was partly supported by the Swiss National Science Foundation, the Hartmann Muller-Stiftung, and the Swiss Foundation for Excellence in Biomedical Research. B.W. is a member of the Clinical Research Priority Program of the University of Zurich on Molecular Imaging. L.F.B. is partly funded by the Fondecyt Grant 1130095. The Centro de Estudios Cientificos CECs is funded by the Chilean Government through the Centers of Excellence Basal Financing Program of CONICYT.

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Mächler, P., Wyss, MT., Elsayed, M., Stobart, J., Gutierrez, R., von Faber-Castell, A., Kaelin, V., Zuend, M., San Martín, A., Romero-Gómez, I., Baeza-Lehnert, F., Lengacher, S., Schneider, BL., Aebischer, P., Magistretti, P. J., Barros, L. F., & Weber, B. (2015). In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons. Cell Metabolism, 23(1), 94-102. https://doi.org/10.1016/j.cmet.2015.10.010

@article{b39c83f2138d40e68b34e03ad360117e,

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. {\textcopyright} 2016 Elsevier Inc.",

author = "Philipp M{\"a}chler and Matthias T. Wyss and Maha Elsayed and Jillian Stobart and Robin Gutierrez and Alexandra von Faber-Castell and Vincens Kaelin and Marc Zuend and Alejandro San Mart{\'i}n and Ignacio Romero-G{\'o}mez and Felipe Baeza-Lehnert and Sylvain Lengacher and Bernard L. Schneider and Patrick Aebischer and Magistretti, {Pierre J.} and L. Felipe Barros and Bruno Weber",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: This research was partly supported by the Swiss National Science Foundation, the Hartmann Muller-Stiftung, and the Swiss Foundation for Excellence in Biomedical Research. B.W. is a member of the Clinical Research Priority Program of the University of Zurich on Molecular Imaging. L.F.B. is partly funded by the Fondecyt Grant 1130095. The Centro de Estudios Cientificos CECs is funded by the Chilean Government through the Centers of Excellence Basal Financing Program of CONICYT.",

year = "2015",

month = nov,

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doi = "10.1016/j.cmet.2015.10.010",

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Mächler, P, Wyss, MT, Elsayed, M, Stobart, J, Gutierrez, R, von Faber-Castell, A, Kaelin, V, Zuend, M, San Martín, A, Romero-Gómez, I, Baeza-Lehnert, F, Lengacher, S, Schneider, BL, Aebischer, P, Magistretti, PJ, Barros, LF & Weber, B 2015, 'In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons', Cell Metabolism, vol. 23, no. 1, pp. 94-102. https://doi.org/10.1016/j.cmet.2015.10.010

TY - JOUR

T1 - In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons

AU - Mächler, Philipp

AU - Wyss, Matthias T.

AU - Elsayed, Maha

AU - Stobart, Jillian

AU - Gutierrez, Robin

AU - von Faber-Castell, Alexandra

AU - Kaelin, Vincens

AU - Zuend, Marc

AU - San Martín, Alejandro

AU - Romero-Gómez, Ignacio

AU - Baeza-Lehnert, Felipe

AU - Lengacher, Sylvain

AU - Schneider, Bernard L.

AU - Aebischer, Patrick

AU - Magistretti, Pierre J.

AU - Barros, L. Felipe

AU - Weber, Bruno

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: This research was partly supported by the Swiss National Science Foundation, the Hartmann Muller-Stiftung, and the Swiss Foundation for Excellence in Biomedical Research. B.W. is a member of the Clinical Research Priority Program of the University of Zurich on Molecular Imaging. L.F.B. is partly funded by the Fondecyt Grant 1130095. The Centro de Estudios Cientificos CECs is funded by the Chilean Government through the Centers of Excellence Basal Financing Program of CONICYT.

PY - 2015/11/19

Y1 - 2015/11/19

N2 - 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.

AB - 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.

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UR - https://linkinghub.elsevier.com/retrieve/pii/S1550413115005264

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U2 - 10.1016/j.cmet.2015.10.010

DO - 10.1016/j.cmet.2015.10.010

M3 - Article

C2 - 26698914

SN - 1550-4131

VL - 23

SP - 94

EP - 102

JO - Cell Metabolism

JF - Cell Metabolism

IS - 1

ER -

In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons

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