Baracchi Francesca, Opp Mark R
Department of Anesthesiology, University of Michigan, 7422 Medical Sciences Building I, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-5615, USA.
Brain Behav Immun. 2008 Aug;22(6):982-93. doi: 10.1016/j.bbi.2008.02.001. Epub 2008 Mar 7.
Data indicate that interleukin (IL)-1 beta and tumor necrosis factor-alpha (TNFalpha) are involved in the regulation of non-rapid eye movement sleep (NREMS). Previous studies demonstrate that mice lacking the IL-1 beta type 1 receptor spend less time in NREMS during the light period, whereas mice lacking the p55 (type 1) receptor for TNFalpha spend less time in NREMS during the dark period. To further investigate roles for IL-1 beta and TNFalpha in sleep regulation we phenotyped sleep and responses to sleep deprivation of mice lacking both the IL-1 beta receptor 1 and TNFalpha receptor 1 (IL-1R1/TNFR1 KO). Male adult mice (IL-1R1/TNFR1 KO, n=14; B6129SF2/J, n=14) were surgically instrumented with EEG electrodes and with a thermistor to measure brain temperature. After recovery and adaptation to the recording apparatus, 48 h of undisturbed baseline recordings were obtained. Mice were then subjected to 6h sleep deprivation at light onset by gentle handling. IL-1R1/TNFR1 KO mice spent less time in NREMS during the last 6h of the dark period and less time in rapid eye movement sleep (REMS) during the light period. There were no differences between strains in the diurnal timing of delta power during NREMS. However, there were strain differences in the relative power spectra of the NREMS EEG during both the light period and the dark period. In addition, during the light period relative power in the theta frequency band of the REMS EEG differed between strains. After sleep deprivation, control mice exhibited prolonged increases in NREMS and REMS, whereas the duration of the NREMS increase was shorter and there was no increase in REMS of IL-1R1/TNFR1 KO mice. Delta power during NREMS increased in both strains after sleep deprivation, but the increase in delta power during NREMS of IL-1R1/TNFR1 KO mice was of greater magnitude and of longer duration than that observed in control mice. These results provide additional evidence that the IL-1 beta and TNFalpha cytokine systems play a role in sleep regulation and in the alterations in sleep that follow prolonged wakefulness.
数据表明，白细胞介素（IL）-1β和肿瘤坏死因子-α（TNFα）参与非快速眼动睡眠（NREMS）的调节。先前的研究表明，缺乏IL-1β1型受体的小鼠在光照期的NREMS时间减少，而缺乏TNFα的p55（1型）受体的小鼠在黑暗期的NREMS时间减少。为了进一步研究IL-1β和TNFα在睡眠调节中的作用，我们对缺乏IL-1β受体1和TNFα受体1（IL-1R1/TNFR1基因敲除）的小鼠的睡眠和对睡眠剥夺的反应进行了表型分析。成年雄性小鼠（IL-1R1/TNFR1基因敲除，n = 14；B6129SF2/J，n = 14）通过手术植入脑电图电极和热敏电阻以测量脑温。恢复并适应记录设备后，获得48小时的无干扰基线记录。然后在光照开始时通过轻柔处理使小鼠经历6小时的睡眠剥夺。IL-1R1/TNFR1基因敲除小鼠在黑暗期的最后6小时内NREMS时间减少，在光照期快速眼动睡眠（REMS）时间减少。在NREMS期间，两品系之间的δ波功率的昼夜节律没有差异。然而，在光照期和黑暗期，NREMS脑电图的相对功率谱存在品系差异。此外，在光照期，REMS脑电图的θ频段相对功率在两品系之间有所不同。睡眠剥夺后，对照小鼠的NREMS和REMS延长增加，而IL-1R1/TNFR1基因敲除小鼠的NREMS增加持续时间较短且REMS没有增加。睡眠剥夺后，两品系NREMS期间的δ波功率均增加，但IL-1R1/TNFR1基因敲除小鼠NREMS期间的δ波功率增加幅度更大且持续时间更长。这些结果提供了额外的证据，表明IL-1β和TNFα细胞因子系统在睡眠调节以及长时间清醒后的睡眠改变中发挥作用。
