title: Circadian regulation of ATP release in astrocytes.
abstract: Circadian clocks sustain daily oscillations in gene expression, physiology, and behavior, relying on transcription-translation feedback loops of clock genes for rhythm generation. Cultured astrocytes display daily oscillations of extracellular ATP, suggesting that ATP release is a circadian output. We hypothesized that the circadian clock modulates ATP release via mechanisms that regulate acute ATP release from glia. To test the molecular basis for circadian ATP release, we developed methods to measure in real-time ATP release and Bmal1::dLuc circadian reporter expression in cortical astrocyte cultures from mice of different genotypes. Daily rhythms of gene expression required functional Clock and Bmal1, both Per1 and Per2, and both Cry1 and Cry2 genes. Similarly, high-level, circadian ATP release also required a functional clock mechanism. Whereas blocking IP(3) signaling significantly disrupted ATP rhythms with no effect on Bmal1::dLuc cycling, blocking vesicular release did not alter circadian ATP release or gene expression. We conclude that astrocytes depend on circadian clock genes and IP(3) signaling to express daily rhythms in ATP release.
authors.affiliation: Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130-4899, USA.
authors.forename: Luciano
authors.initials: L
authors.lastname: Marpegan
authors.forename: Adrienne E
authors.initials: AE
authors.lastname: Swanstrom
authors.forename: Kevin
authors.initials: K
authors.lastname: Chung
authors.forename: Tatiana
authors.initials: T
authors.lastname: Simon
authors.forename: Philip G
authors.initials: PG
authors.lastname: Haydon
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Khan
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Liu
authors.forename: Erik D
authors.initials: ED
authors.lastname: Herzog
authors.forename: Christian
authors.initials: C
authors.lastname: Beaulé
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D056931:Cryptochromes / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D056926:CLOCK Proteins; C538944:Clock protein, mouse