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Arousal-induced cortical activity triggers lactate release from astrocytes


Zuend, Marc; Saab, Aiman S; Wyss, Matthias T; Ferrari, Kim David; Hösli, Ladina; Looser, Zoe J; Stobart, Jillian L; Duran, Jordi; Guinovart, Joan J; Barros, L Felipe; Weber, Bruno (2020). Arousal-induced cortical activity triggers lactate release from astrocytes. Nature Metabolism, 2(2):179-191.

Abstract

It has been suggested that, in states of arousal, release of noradrenaline and β-adrenergic signalling affect long-term memory formation by stimulating astrocytic lactate production from glycogen. However, the temporal relationship between cortical activity and cellular lactate fluctuations upon changes in arousal remains to be fully established. Also, the role of β-adrenergic signalling and brain glycogen metabolism on neural lactate dynamics in vivo is still unknown. Here, we show that an arousal-induced increase in cortical activity triggers lactate release into the extracellular space, and this correlates with a fast and prominent lactate dip in astrocytes. The immediate drop in astrocytic lactate concentration and the parallel increase in extracellular lactate levels underline an activity-dependent lactate release from astrocytes. Moreover, when β-adrenergic signalling is blocked or the brain is depleted of glycogen, the arousal-evoked cellular lactate surges are significantly reduced. We provide in vivo evidence that cortical activation upon arousal triggers lactate release from astrocytes, a rise in intracellular lactate levels mediated by β-adrenergic signalling and the mobilization of lactate from glycogen stores.

Abstract

It has been suggested that, in states of arousal, release of noradrenaline and β-adrenergic signalling affect long-term memory formation by stimulating astrocytic lactate production from glycogen. However, the temporal relationship between cortical activity and cellular lactate fluctuations upon changes in arousal remains to be fully established. Also, the role of β-adrenergic signalling and brain glycogen metabolism on neural lactate dynamics in vivo is still unknown. Here, we show that an arousal-induced increase in cortical activity triggers lactate release into the extracellular space, and this correlates with a fast and prominent lactate dip in astrocytes. The immediate drop in astrocytic lactate concentration and the parallel increase in extracellular lactate levels underline an activity-dependent lactate release from astrocytes. Moreover, when β-adrenergic signalling is blocked or the brain is depleted of glycogen, the arousal-evoked cellular lactate surges are significantly reduced. We provide in vivo evidence that cortical activation upon arousal triggers lactate release from astrocytes, a rise in intracellular lactate levels mediated by β-adrenergic signalling and the mobilization of lactate from glycogen stores.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Endocrinology, Diabetes and Metabolism
Health Sciences > Physiology (medical)
Health Sciences > Internal Medicine
Life Sciences > Cell Biology
Language:English
Date:1 February 2020
Deposited On:21 Jan 2021 13:19
Last Modified:28 Jan 2021 15:42
Publisher:Nature Publishing Group
ISSN:2522-5812
OA Status:Green
Publisher DOI:https://doi.org/10.1038/s42255-020-0170-4
PubMed ID:32694692

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