Womac Alisa D, Burkeen Jeff F, Neuendorff Nichole, Earnest David J, Zoran Mark J
Department of Biology and Center for Research on Biological Clocks, Texas A&M University, College Station, TX, USA.
Eur J Neurosci. 2009 Sep;30(5):869-76. doi: 10.1111/j.1460-9568.2009.06874.x. Epub 2009 Aug 27.
The master circadian pacemaker located within the suprachiasmatic nucleus (SCN) of the mammalian brain controls system-level rhythms in animal physiology. Specific SCN outputs synchronize circadian physiological rhythms in other brain regions. Within the SCN, communication among neural cells provides for the coordination of autonomous cellular oscillations into ensemble rhythms. ATP is a neural transmitter involved in local communication among astrocytes and between astrocytes and neurons. Using a luciferin-luciferase chemiluminescence assay, we have demonstrated that ATP levels fluctuate rhythmically within both SCN2.2 cell cultures and the rat SCN in vivo. SCN2.2 cells generated circadian oscillations in both the production and extracellular accumulation of ATP. Circadian fluctuations in ATP accumulation persisted with an average period (tau) of 23.7 h in untreated as well as vehicle-treated and forskolin-treated SCN2.2 cells, indicating that treatment with an inductive stimulus is not necessary to propagate these rhythms. ATP levels in the rat SCN in vivo were marked by rhythmic variation during exposure to 12 h of light and 12 h of dark or constant darkness, with peak accumulation occurring during the latter half of the dark phase or subjective night. Primary cultures of cortical astrocytes similarly expressed circadian oscillations in extracellular ATP accumulation that persisted for multiple cycles with periods of about 23 h. These results suggest that circadian oscillations in extracellular ATP levels represent a physiological output of the mammalian cellular clock, common to the SCN pacemaker and astrocytes from at least some brain regions, and thus may provide a mechanism for clock control of gliotransmission between astrocytes and to neurons.
位于哺乳动物大脑视交叉上核（SCN）内的主昼夜节律起搏器控制着动物生理系统层面的节律。特定的SCN输出使其他脑区的昼夜生理节律同步。在SCN内，神经细胞之间的通讯可将自主细胞振荡协调为整体节律。ATP是一种神经递质，参与星形胶质细胞之间以及星形胶质细胞与神经元之间的局部通讯。我们使用荧光素 - 荧光素酶化学发光测定法证明，在SCN2.2细胞培养物和大鼠体内SCN中，ATP水平均有节律性波动。SCN2.2细胞在ATP的产生和细胞外积累方面都产生了昼夜振荡。在未处理以及用载体处理和福斯高林处理的SCN2.2细胞中，ATP积累的昼夜波动持续存在，平均周期（tau）为23.7小时，这表明不需要用诱导刺激来传播这些节律。在大鼠体内SCN中，当暴露于12小时光照和12小时黑暗或持续黑暗时，ATP水平有节律性变化，在黑暗期后半段或主观夜间出现积累峰值。皮质星形胶质细胞的原代培养物在细胞外ATP积累方面同样表现出昼夜振荡，这种振荡持续多个周期，周期约为23小时。这些结果表明，细胞外ATP水平的昼夜振荡代表了哺乳动物细胞时钟的一种生理输出，这是SCN起搏器和至少一些脑区的星形胶质细胞共有的，因此可能为星形胶质细胞与神经元之间神经胶质传递的时钟控制提供一种机制。
