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Adenosine signalling to astrocytes coordinates brain metabolism and function

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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Adenosine signalling to astrocytes coordinates brain metabolism and function. / Theparambil, Shefeeq M; Kopach, Olga; Braga, Alice et al.
In: Nature, Vol. 632, No. 8023, 01.08.2024, p. 139-146.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Theparambil, SM, Kopach, O, Braga, A, Nizari, S, Hosford, PS, Sagi-Kiss, V, Hadjihambi, A, Konstantinou, C, Esteras, N, Gutierrez Del Arroyo, A, Ackland, GL, Teschemacher, AG, Dale, N, Eckle, T, Andrikopoulos, P, Rusakov, DA, Kasparov, S & Gourine, AV 2024, 'Adenosine signalling to astrocytes coordinates brain metabolism and function', Nature, vol. 632, no. 8023, pp. 139-146. https://doi.org/10.1038/s41586-024-07611-w

APA

Theparambil, S. M., Kopach, O., Braga, A., Nizari, S., Hosford, P. S., Sagi-Kiss, V., Hadjihambi, A., Konstantinou, C., Esteras, N., Gutierrez Del Arroyo, A., Ackland, G. L., Teschemacher, A. G., Dale, N., Eckle, T., Andrikopoulos, P., Rusakov, D. A., Kasparov, S., & Gourine, A. V. (2024). Adenosine signalling to astrocytes coordinates brain metabolism and function. Nature, 632(8023), 139-146. https://doi.org/10.1038/s41586-024-07611-w

Vancouver

Theparambil SM, Kopach O, Braga A, Nizari S, Hosford PS, Sagi-Kiss V et al. Adenosine signalling to astrocytes coordinates brain metabolism and function. Nature. 2024 Aug 1;632(8023):139-146. Epub 2024 Jul 3. doi: 10.1038/s41586-024-07611-w

Author

Theparambil, Shefeeq M ; Kopach, Olga ; Braga, Alice et al. / Adenosine signalling to astrocytes coordinates brain metabolism and function. In: Nature. 2024 ; Vol. 632, No. 8023. pp. 139-146.

Bibtex

@article{a171168d93f349d68cfae2cee24e4730,
title = "Adenosine signalling to astrocytes coordinates brain metabolism and function",
abstract = "Brain computation performed by billions of nerve cells relies on a sufficient and uninterrupted nutrient and oxygen supply . Astrocytes, the ubiquitous glial neighbours of neurons, govern brain glucose uptake and metabolism , but the exact mechanisms of metabolic coupling between neurons and astrocytes that ensure on-demand support of neuronal energy needs are not fully understood . Here we show, using experimental in vitro and in vivo animal models, that neuronal activity-dependent metabolic activation of astrocytes is mediated by neuromodulator adenosine acting on astrocytic A2B receptors. Stimulation of A2B receptors recruits the canonical cyclic adenosine 3',5'-monophosphate-protein kinase A signalling pathway, leading to rapid activation of astrocyte glucose metabolism and the release of lactate, which supplements the extracellular pool of readily available energy substrates. Experimental mouse models involving conditional deletion of the gene encoding A2B receptors in astrocytes showed that adenosine-mediated metabolic signalling is essential for maintaining synaptic function, especially under conditions of high energy demand or reduced energy supply. Knockdown of A2B receptor expression in astrocytes led to a major reprogramming of brain energy metabolism, prevented synaptic plasticity in the hippocampus, severely impaired recognition memory and disrupted sleep. These data identify the adenosine A2B receptor as an astrocytic sensor of neuronal activity and show that cAMP signalling in astrocytes tunes brain energy metabolism to support its fundamental functions such as sleep and memory. ",
keywords = "Adenosine/metabolism, Animals, Astrocytes/metabolism, Brain/metabolism, Cyclic AMP-Dependent Protein Kinases/metabolism, Cyclic AMP/metabolism, Energy Metabolism, Female, Glucose/metabolism, Hippocampus/metabolism, Lactic Acid/metabolism, Male, Mice, Mice, Inbred C57BL, Neuronal Plasticity, Neurons/metabolism, Rats, Receptor, Adenosine A2B/deficiency, Recognition, Psychology/physiology, Signal Transduction, Sleep/genetics, Synapses/metabolism",
author = "Theparambil, {Shefeeq M} and Olga Kopach and Alice Braga and Shereen Nizari and Hosford, {Patrick S} and Virag Sagi-Kiss and Anna Hadjihambi and Christos Konstantinou and Noemi Esteras and {Gutierrez Del Arroyo}, Ana and Ackland, {Gareth L} and Teschemacher, {Anja G} and Nicholas Dale and Tobias Eckle and Petros Andrikopoulos and Rusakov, {Dmitri A} and Sergey Kasparov and Gourine, {Alexander V}",
year = "2024",
month = aug,
day = "1",
doi = "10.1038/s41586-024-07611-w",
language = "English",
volume = "632",
pages = "139--146",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "8023",

}

RIS

TY - JOUR

T1 - Adenosine signalling to astrocytes coordinates brain metabolism and function

AU - Theparambil, Shefeeq M

AU - Kopach, Olga

AU - Braga, Alice

AU - Nizari, Shereen

AU - Hosford, Patrick S

AU - Sagi-Kiss, Virag

AU - Hadjihambi, Anna

AU - Konstantinou, Christos

AU - Esteras, Noemi

AU - Gutierrez Del Arroyo, Ana

AU - Ackland, Gareth L

AU - Teschemacher, Anja G

AU - Dale, Nicholas

AU - Eckle, Tobias

AU - Andrikopoulos, Petros

AU - Rusakov, Dmitri A

AU - Kasparov, Sergey

AU - Gourine, Alexander V

PY - 2024/8/1

Y1 - 2024/8/1

N2 - Brain computation performed by billions of nerve cells relies on a sufficient and uninterrupted nutrient and oxygen supply . Astrocytes, the ubiquitous glial neighbours of neurons, govern brain glucose uptake and metabolism , but the exact mechanisms of metabolic coupling between neurons and astrocytes that ensure on-demand support of neuronal energy needs are not fully understood . Here we show, using experimental in vitro and in vivo animal models, that neuronal activity-dependent metabolic activation of astrocytes is mediated by neuromodulator adenosine acting on astrocytic A2B receptors. Stimulation of A2B receptors recruits the canonical cyclic adenosine 3',5'-monophosphate-protein kinase A signalling pathway, leading to rapid activation of astrocyte glucose metabolism and the release of lactate, which supplements the extracellular pool of readily available energy substrates. Experimental mouse models involving conditional deletion of the gene encoding A2B receptors in astrocytes showed that adenosine-mediated metabolic signalling is essential for maintaining synaptic function, especially under conditions of high energy demand or reduced energy supply. Knockdown of A2B receptor expression in astrocytes led to a major reprogramming of brain energy metabolism, prevented synaptic plasticity in the hippocampus, severely impaired recognition memory and disrupted sleep. These data identify the adenosine A2B receptor as an astrocytic sensor of neuronal activity and show that cAMP signalling in astrocytes tunes brain energy metabolism to support its fundamental functions such as sleep and memory.

AB - Brain computation performed by billions of nerve cells relies on a sufficient and uninterrupted nutrient and oxygen supply . Astrocytes, the ubiquitous glial neighbours of neurons, govern brain glucose uptake and metabolism , but the exact mechanisms of metabolic coupling between neurons and astrocytes that ensure on-demand support of neuronal energy needs are not fully understood . Here we show, using experimental in vitro and in vivo animal models, that neuronal activity-dependent metabolic activation of astrocytes is mediated by neuromodulator adenosine acting on astrocytic A2B receptors. Stimulation of A2B receptors recruits the canonical cyclic adenosine 3',5'-monophosphate-protein kinase A signalling pathway, leading to rapid activation of astrocyte glucose metabolism and the release of lactate, which supplements the extracellular pool of readily available energy substrates. Experimental mouse models involving conditional deletion of the gene encoding A2B receptors in astrocytes showed that adenosine-mediated metabolic signalling is essential for maintaining synaptic function, especially under conditions of high energy demand or reduced energy supply. Knockdown of A2B receptor expression in astrocytes led to a major reprogramming of brain energy metabolism, prevented synaptic plasticity in the hippocampus, severely impaired recognition memory and disrupted sleep. These data identify the adenosine A2B receptor as an astrocytic sensor of neuronal activity and show that cAMP signalling in astrocytes tunes brain energy metabolism to support its fundamental functions such as sleep and memory.

KW - Adenosine/metabolism

KW - Animals

KW - Astrocytes/metabolism

KW - Brain/metabolism

KW - Cyclic AMP-Dependent Protein Kinases/metabolism

KW - Cyclic AMP/metabolism

KW - Energy Metabolism

KW - Female

KW - Glucose/metabolism

KW - Hippocampus/metabolism

KW - Lactic Acid/metabolism

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Neuronal Plasticity

KW - Neurons/metabolism

KW - Rats

KW - Receptor, Adenosine A2B/deficiency

KW - Recognition, Psychology/physiology

KW - Signal Transduction

KW - Sleep/genetics

KW - Synapses/metabolism

U2 - 10.1038/s41586-024-07611-w

DO - 10.1038/s41586-024-07611-w

M3 - Journal article

C2 - 38961289

VL - 632

SP - 139

EP - 146

JO - Nature

JF - Nature

SN - 0028-0836

IS - 8023

ER -