dc.contributor.author | Theparambil, SM | en_US |
dc.contributor.author | Kopach, O | en_US |
dc.contributor.author | Braga, A | en_US |
dc.contributor.author | Nizari, S | en_US |
dc.contributor.author | Hosford, PS | en_US |
dc.contributor.author | Sagi-Kiss, V | en_US |
dc.contributor.author | Hadjihambi, A | en_US |
dc.contributor.author | Konstantinou, C | en_US |
dc.contributor.author | Esteras, N | en_US |
dc.contributor.author | Gutierrez Del Arroyo, A | en_US |
dc.contributor.author | Ackland, GL | en_US |
dc.contributor.author | Teschemacher, AG | en_US |
dc.contributor.author | Dale, N | en_US |
dc.contributor.author | Eckle, T | en_US |
dc.contributor.author | Andrikopoulos, P | en_US |
dc.contributor.author | Rusakov, DA | en_US |
dc.contributor.author | Kasparov, S | en_US |
dc.contributor.author | Gourine, AV | en_US |
dc.date.accessioned | 2024-07-09T11:08:19Z | |
dc.date.available | 2024-05-27 | en_US |
dc.date.issued | 2024-07-03 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/97936 | |
dc.description.abstract | Brain computation performed by billions of nerve cells relies on a sufficient and uninterrupted nutrient and oxygen supply1,2. Astrocytes, the ubiquitous glial neighbours of neurons, govern brain glucose uptake and metabolism3,4, but the exact mechanisms of metabolic coupling between neurons and astrocytes that ensure on-demand support of neuronal energy needs are not fully understood5,6. 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. | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Nature | en_US |
dc.rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | |
dc.title | Adenosine signalling to astrocytes coordinates brain metabolism and function. | en_US |
dc.type | Article | |
dc.rights.holder | © 2024, The Author(s) | |
dc.identifier.doi | 10.1038/s41586-024-07611-w | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/38961289 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
dcterms.dateAccepted | 2024-05-27 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
qmul.funder | Personalised perioperative medicine to enhance recovery after major surgery.::National Institute for Health and Care Research | en_US |
rioxxterms.funder.project | b215eee3-195d-4c4f-a85d-169a4331c138 | en_US |