School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia.
Department of Pharmacology and Toxicology, Institute of Pharmacy and CMBI, University of Innsbruck, Innsbruck, Austria.
FASEB J. 2021 Feb;35(2):e21195. doi: 10.1096/fj.202001555RR. Epub 2020 Nov 16.
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.
小胶质细胞是中枢神经系统的关键神经免疫细胞，其功能最广为人知的是在抵御病原体和损伤方面。最近的发现，包括我们自己的发现，表明小胶质细胞还有几种免疫独立的功能，包括调节饱腹感、促进记忆和调节疼痛反应。这些与小胶质细胞相关的功能中有许多受昼夜节律的影响，因此，根据一天中的时间而有很大的变化。为了更深入地了解这种联系，我们使用了 Cx3cr1-Dtr 转基因 Wistar 大鼠模型来急性耗尽小胶质细胞，并检查这是否会导致昼夜温度、代谢和活动测量的中断。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的表达变化相对应。我们的数据表明，在没有小胶质细胞的情况下，几个与非活动期有关的昼夜节律明显中断，伴随着昼夜节律调节基因和蛋白的变化。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昼夜节律紊乱（如轮班工作或时差）具有令人兴奋的潜力。
