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.
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.