期刊
JOURNAL OF NEUROSCIENCE
卷 31, 期 23, 页码 8342-8350出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.6537-10.2011
关键词
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资金
- NIMH [63104]
- NIH [P30 NS057105]
- Division Of Integrative Organismal Systems
- Direct For Biological Sciences [0920417] Funding Source: National Science Foundation
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 IP3 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 IP3 signaling to express daily rhythms in ATP release.
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