title: Astrocyte-derived adenosine modulates increased sleep pressure during inflammatory response.
abstract: Activation of the immune system elicits several behavioral changes collectively called sickness. Among the behavioral changes, systemic infections induce an increase in time spent in nonrapid-eye-movement (NREM) sleep and an increase of slow wave activity (or "sleep pressure"). Using an inducible, astrocyte-specific transgenic dominant negative SNARE (dnSNARE) mouse line we recently demonstrated that gliotransmission plays an important role in sleep homeostasis through an adenosine receptor 1 (A1R)-sensitive pathway. It has been hypothesized that systemic infection, mimicked by peripheral administration of lipopolysaccharide (LPS), increases sleeping behavior in part through upregulation of central adenosine levels. Moreover, as a source of immunologically relevant factors, astrocytes play a pivotal role in the central nervous system immune and inflammatory responses. However, little is known about the role of astrocytes in the CNS response to a peripheral immune challenge. We hypothesize that LPS impacts sleep homeostasis through the modulation of astrocyte-derived adenosine accumulation. We therefore used dnSNARE mice to determine whether astrocytes contribute to the increased sleep pressure under immune challenge and whether this is a result of changes in adenosine signaling. We demonstrate that dnSNARE-mediated gliotransmission is required for the ability of LPS to elevate sleep pressure as measured by the power of slow wave activity during NREM sleep. Moreover, in agreement with a role of astrocyte-derived adenosine in modulating sleep homeostasis, we find that intracerebroventricular infusion of the A1R antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) mimics this dnSNARE phenotype. Taken together, our data demonstrate that astrocytic adenosine acting through A1 receptors contributes to the modulation of sleep pressure by LPS.
authors: Laboratory of Nutrition and Integrative Neurobiology, University of Bordeaux, UMR 1286, Bordeaux, France. agnes.nadjar@u-bordeaux2.fr
authors: Agnes
authors: A
authors: Nadjar
authors: Tamara
authors: T
authors: Blutstein
authors: Agnes
authors: A
authors: Aubert
authors: Sophie
authors: S
authors: Laye
authors: Philip G
authors: PG
authors: Haydon
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004569:Electroencephalography / Q000379:methods; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D043682:Receptor, Adenosine A1 / Q000502:physiology; D050600:SNARE Proteins / Q000096:biosynthesis / Q000235:genetics; D012890:Sleep / Q000187:drug effects / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides; D043682:Receptor, Adenosine A1; D050600:SNARE Proteins; D000241:Adenosine