In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons
| Autor: | Alejandro San Martín, Robin Gutiérrez, Felipe Baeza-Lehnert, Maha Elsayed, Patrick Aebischer, Matthias T. Wyss, Vincens Kaelin, Marc Zuend, Jillian L. Stobart, Sylvain Lengacher, Philipp Mächler, Bernard L. Schneider, Ignacio Romero-Gómez, Alexandra von Faber-Castell, Bruno Weber, Pierre J. Magistretti, L. Felipe Barros |
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| Přispěvatelé: | University of Zurich, Weber, Bruno |
| Předmět: |
0301 basic medicine
Physiology Confocal 10050 Institute of Pharmacology and Toxicology 610 Medicine & health Brain tissue Lactate Injection 1307 Cell Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo 1312 Molecular Biology Animals Lactic Acid 10064 Neuroscience Center Zurich Molecular Biology Monocarboxylate transporter Neurons Microscopy Confocal biology Brain Cell Biology 1314 Physiology Lactic acid Cell biology Mice Inbred C57BL 030104 developmental biology chemistry Biochemistry Permeability (electromagnetism) Astrocytes biology.protein 570 Life sciences Female Energy Metabolism 030217 neurology & neurosurgery Intracellular |
| Zdroj: | Cell metabolism Cell Metabolism Artículos CONICYT CONICYT Chile instacron:CONICYT |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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