Al Maghribi Abrar, Ottaway Caitlin, Rempe Michael, Medina Elizabeth, Ford Kaitlyn, Singletary Kristan, Peixoto Lucia
Department of Translational Medicine and Physiology, Sleep and Performance Research Center, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA.
Washington University School of Medicine, St Louis, MO, USA.
Neurobiol Sleep Circadian Rhythms. 2025 Jun 11;19:100132. doi: 10.1016/j.nbscr.2025.100132. eCollection 2025 Nov.
Rett syndrome (RTT) is a severe, progressive neurodevelopmental disorder caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (). Sleep problems are frequently reported in Rett Syndrome, but the exact nature remains relatively unexplored. Currently there is limited understanding of MECP2's role in sleep architecture and regulation. In this study, we employed longitudinal electroencephalographic (EEG) and electromyographic (EMG) recordings to investigate sleep architecture during baseline conditions as well as the homeostatic response to sleep deprivation (SD) in 2 male mice. At baseline, 2 mice have more non-rapid-eye-movement (NREM) sleep and less rapid-eye-movement (REM) sleep than their wildtype littermates during the light period. However, 2 mice display altered sleep timing during the dark period, spending more time in both NREM and REM during the first half and less time during the second half. 2 mice also have lower EEG spectral power during wake and NREM at higher frequencies and higher power at lower frequencies during REM in compared to wildtype mice. In response to SD, 2 mice can accumulate and discharge sleep pressure normally and show a sleep rebound. However, baseline differences in sleep architecture are heightened after SD. Overall, our findings show that RTT mice exhibit distinct sleep patterns compared to wildtype mice, with time-of-day-dependent variations in NREM and REM sleep, as well as altered EEG spectral properties, that become more pronounced following SD. Future research should explore the molecular mechanisms through which MECP2 regulates sleep architecture to develop targeted therapeutics for sleep disturbances in RTT patients.
雷特综合征（RTT）是一种严重的、进行性的神经发育障碍，由编码甲基-CpG结合蛋白2（MECP2）的X连锁基因突变引起。睡眠问题在雷特综合征中经常被报道，但确切性质仍相对未被探索。目前对MECP2在睡眠结构和调节中的作用了解有限。在本研究中，我们采用纵向脑电图（EEG）和肌电图（EMG）记录来研究2只雄性小鼠在基线条件下的睡眠结构以及对睡眠剥夺（SD）的稳态反应。在基线时，2只小鼠在光照期比其野生型同窝小鼠有更多的非快速眼动（NREM）睡眠和更少的快速眼动（REM）睡眠。然而，2只小鼠在黑暗期的睡眠时间发生了改变，在前半段NREM和REM睡眠中花费的时间更多，后半段花费的时间更少。与野生型小鼠相比，2只小鼠在清醒和NREM期间高频时的EEG频谱功率较低，在REM期间低频时的功率较高。对SD的反应中，2只小鼠能够正常积累和释放睡眠压力并表现出睡眠反弹。然而，SD后睡眠结构的基线差异加剧。总体而言，我们的研究结果表明，与野生型小鼠相比，RTT小鼠表现出独特的睡眠模式，NREM和REM睡眠存在时间依赖性变化，以及EEG频谱特性改变，在SD后变得更加明显。未来的研究应探索MECP2调节睡眠结构的分子机制，以开发针对RTT患者睡眠障碍的靶向治疗方法。
