Microglia, the key neuroimmune cells of the central nervous system, are best known for their function in defending an individual from pathogens and injury. Recent findings, including our own, suggest microglia also have several immune-independent roles, including in regulating satiety, promoting memory, and modifying pain responses. Many of these microglia-associated functions are affected by circadian rhythmicity, thus, varying substantially depending upon the time of day. To gain further insight into this link, we used a Cx3cr1-Dtr transgenic Wistar rat model to acutely deplete microglia and examined if this could lead to a disruption in diurnal temperature, metabolism, and activity measures. We also examined if differences in the physiological rhythms corresponded with changes in the expression of key circadian rhythm-regulating genes and proteins. Our data show that in the absence of microglia there is a pronounced disruption of diurnal rhythms in several domains consistent with a shift toward the inactive phase, in conjunction with changes in circadian rhythm-regulating genes and proteins. These data suggest microglia are involved in the regulation of circadian rhythms and indicate an exciting potential to manipulate these cells to improve disrupted circadian rhythms such as with shift-work or jet-lag.

中文翻译：

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大鼠小胶质细胞消融扰乱昼夜节律系统


小胶质细胞是中枢神经系统的关键神经免疫细胞，以其保护个体免受病原体和损伤的功能而闻名。最近的研究结果（包括我们自己的研究结果）表明，小胶质细胞还具有多种与免疫无关的作用，包括调节饱腹感、促进记忆和改变疼痛反应。许多与小胶质细胞相关的功能都受到昼夜节律的影响，因此，根据一天中的时间而有很大的变化。为了进一步了解这种联系，我们使用 Cx3cr1-Dtr 转基因 Wistar 大鼠模型来急剧消耗小胶质细胞，并检查这是否会导致昼夜温度、新陈代谢和活动测量的破坏。我们还检查了生理节律的差异是否与关键昼夜节律调节基因和蛋白质的表达变化相对应。我们的数据表明，在小胶质细胞缺失的情况下，几个领域的昼夜节律明显受到破坏，这与向非活动期的转变相一致，同时昼夜节律调节基因和蛋白质也发生了变化。这些数据表明小胶质细胞参与昼夜节律的调节，并表明操纵这些细胞以改善被破坏的昼夜节律（例如轮班工作或时差反应）的令人兴奋的潜力。