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Adenosine signalling to astrocytes coordinates brain metabolism and function

Shefeeq M. Theparambil, Olga Kopach, Alice Braga, Shereen Nizari, Patrick S. Hosford, Virag Sagi-Kiss, Anna Hadjihambi, Christos Konstantinou, Noemi Esteras, Ana Gutierrez Del Arroyo, Gareth L. Ackland, Anja G. Teschemacher, Nicholas Dale, Tobias Eckle, Petros Andrikopoulos, Dmitri A. Rusakov, Sergey Kasparov & Alexander V. Gourine

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. The data identifies 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.

Nature. July 2024


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