title: Astrocyte-derived adenosine is central to the hypnogenic effect of glucose.
abstract: Sleep has been hypothesised to maintain a close relationship with metabolism. Here we focus on the brain structure that triggers slow-wave sleep, the ventrolateral preoptic nucleus (VLPO), to explore the cellular and molecular signalling pathways recruited by an increase in glucose concentration. We used infrared videomicroscopy on ex vivo brain slices to establish that glucose induces vasodilations specifically in the VLPO via the astrocytic release of adenosine. Real-time detection by in situ purine biosensors further revealed that the adenosine level doubles in response to glucose, and triples during the wakefulness period. Finally, patch-clamp recordings uncovered the depolarizing effect of adenosine and its A2A receptor agonist, CGS-21680, on sleep-promoting VLPO neurons. Altogether, our results provide new insights into the metabolically driven release of adenosine. We hypothesise that adenosine adjusts the local energy supply to local neuronal activity in response to glucose. This pathway could contribute to sleep-wake transition and sleep intensity.
authors.affiliation: Brain Plasticity Unit, ESPCI-ParisTech, PSL Research University, Paris, F-75005, France.|CNRS, UMR 8249, Paris, F-75005, France.
authors.forename: Emeric
authors.initials: E
authors.lastname: Scharbarg
authors.affiliation: Brain Plasticity Unit, ESPCI-ParisTech, PSL Research University, Paris, F-75005, France.|CNRS, UMR 8249, Paris, F-75005, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Daenens
authors.affiliation: Ecole Normale Supérieure-PSL Research University, Département de Chimie, Sorbonne Universités - UPMC Univ Paris 06, Paris, F-75005, France.|CNRS, UMR 8640 Pasteur, Paris, F-75005, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lemaître
authors.affiliation: Brain Plasticity Unit, ESPCI-ParisTech, PSL Research University, Paris, F-75005, France.|CNRS, UMR 8249, Paris, F-75005, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Geoffroy
authors.affiliation: Ecole Normale Supérieure-PSL Research University, Département de Chimie, Sorbonne Universités - UPMC Univ Paris 06, Paris, F-75005, France.|CNRS, UMR 8640 Pasteur, Paris, F-75005, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Guille-Collignon
authors.affiliation: Brain Plasticity Unit, ESPCI-ParisTech, PSL Research University, Paris, F-75005, France.|CNRS, UMR 8249, Paris, F-75005, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Gallopin
authors.affiliation: Brain Plasticity Unit, ESPCI-ParisTech, PSL Research University, Paris, F-75005, France.|CNRS, UMR 8249, Paris, F-75005, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Rancillac
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015374:Biosensing Techniques; D005110:Extracellular Space / Q000737:chemistry; D005947:Glucose / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology; D043705:Receptor, Adenosine A2A; D012890:Sleep / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D043705:Receptor, Adenosine A2A; D005947:Glucose; D000241:Adenosine; D009638:Norepinephrine