circadian modulation of gene expression, but not glutamate uptake, in mouse and rat cortical astrocytes生理调节的基因表达,但不是谷氨酸摄取,在小鼠和大鼠大脑皮质星形胶质细胞.pdfVIP

Circadian Modulation of Gene Expression, but not Glutamate Uptake, in Mouse and Rat Cortical Astrocytes ´ ´ ¤ Christian Beaule, Adrienne Swanstrom, Marıa Juliana Leone , Erik D. Herzog* Department of Biology, Washington University, Saint Louis, Missouri, United States of America Abstract Background: Circadian clocks control daily rhythms including sleep-wake, hormone secretion, and metabolism. These clocks are based on intracellular transcription-translation feedback loops that sustain daily oscillations of gene expression in many cell types. Mammalian astrocytes display circadian rhythms in the expression of the clock genes Period1 (Per1) and Period2 (Per2). However, a functional role for circadian oscillations in astrocytes is unknown. Because uptake of extrasynaptic glutamate depends on the presence of Per2 in astrocytes, we asked whether glutamate uptake by glia is circadian. Methodology/Principal Findings: We measured glutamate uptake, transcript and protein levels of the astrocyte-specific glutamate transporter, Glast, and the expression of Per1 and Per2 from cultured cortical astrocytes and from explants of somatosensory cortex. We found that glutamate uptake and Glast mRNA and protein expression were significantly reduced in Clock/Clock, Per2- or NPAS2-deficient glia. Uptake was augmented when the medium was supplemented with dibutyryl- cAMP or B27. Critically, glutamate uptake was not circadian in cortical astrocytes cultured from rats or mice or in cortical slices from mice. Conclusion/Significance: We conclude that glutamate uptake levels are modulated by CLOCK, PER2, NPAS2,