Circadian rhythm generation and entrainment in astrocytes.
In mammals, the master circadian pacemaker is considered the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN consists of a heterogeneous population of neurons and relatively understudied glia. We investigated whether glia, like neurons, rhythmically express circadian genes. We generated pure cultures of cortical astrocytes from Period2::luciferase (Per2::luc) knock-in mice and Period1::luciferase (Per1::luc) transgenic rats and recorded bioluminescence as a real-time reporter of gene activity. We found that rat Per1::luc and mouse Per2::luc astroglia express circadian rhythms with a genetically determined period. These rhythms damped out after several days but were reinitiated by a variety of treatments, including a full volume exchange of the medium. If cultures were treated before damping out, the phase of Per1::luc rhythmicity was shifted, depending on the time of the pulse relative to the peak of Per1 expression. Glial rhythms entrained to daily 1.5 degrees C temperature cycles and were significantly sustained when cocultured with explants of the adult SCN but not with cortical explants. Thus, multiple signals, including a diffusible factor(s) from the SCN, are sufficient to either entrain or restart circadian oscillations in cortical glia.
Prolo
Laura M
LM
Department of Biology, Washington University, St. Louis, Missouri 63130-4899, USA.
Takahashi
Joseph S
JS
Herzog
Erik D
ED
D000818:Animals; D030801:Animals, Genetically Modified; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology*; D001683:Biological Clocks / Q000502:physiology*; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002940:Circadian Rhythm / Q000502:physiology*; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000502:physiology; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C539024:Per1 protein, rat; C513312:Per2 protein, mouse; C513311:Per2 protein, rat; D056950:Period Circadian Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D008156:Luciferases