Yang Weiwen, Shi Jingyi, Li Chenggang, Yang Jingqun, Yu Jianjun, Huang Juan, Rao Yi
Chinese Institute of Brain Research, Beijing (CIBR), and Chinese Institutes for Medical Research, Beijing (CIMR), Capital Medical University, Beijing, China.
Laboratory of Neurochemical Biology, Peking-Tsinghua-NIBS (PTN) Graduate Program, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, PKU-IDG/McGovern Institute for Brain Research, School of Life Sciences; Department of Chemical Biology, College of Chemistry and Chemical Engineering; School of Pharmaceutical Sciences at the Health Sciences Center, Peking University, Beijing, China.
Commun Biol. 2025 Jan 5;8(1):11. doi: 10.1038/s42003-024-07449-y.
While sleep is important, our understanding of its molecular mechanisms is limited. Over the last two decades, protein kinases including Ca/calmodulin-dependent protein kinase II (CaMKII) α and β have been implicated in sleep regulation. Of all the known mouse genetic mutants, the biggest changes in sleep is reported to be observed in adult mice with sgRNAs for Camk2b injected into their embryos: sleep is reduced by approximately 120 min (mins) over 24 h (hrs). We have reexamined the sleep phenotype in mice with either Camk2a or Camk2b gene knocked-out by conventional gene targetting. While the basal sleep is reduced in Camk2a knockout mice, it remains unaltered in Camk2b mutants. Knockout of either Camk2a or Camk2b reduces sleep rebound after deprivation, indicating their roles in sleep homeostasis. These results indicate the involvement of CaMKIIα in both basal sleep and sleep homeostasis while CaMKIIβ is mainly required physiologically for sleep homeostasis, serving as a stimulus for rigorous studies in the future.
虽然睡眠很重要，但我们对其分子机制的了解有限。在过去的二十年里，包括钙/钙调蛋白依赖性蛋白激酶II（CaMKII）α和β在内的蛋白激酶已被证明与睡眠调节有关。在所有已知的小鼠基因变异体中，据报道，在胚胎期注射针对Camk2b的sgRNA的成年小鼠中观察到睡眠变化最大：24小时内睡眠减少约120分钟。我们重新检查了通过传统基因靶向敲除Camk2a或Camk2b基因的小鼠的睡眠表型。虽然Camk2a基因敲除小鼠的基础睡眠减少，但Camk2b基因变异体中的基础睡眠保持不变。敲除Camk2a或Camk2b都会减少剥夺后的睡眠反弹，表明它们在睡眠稳态中的作用。这些结果表明CaMKIIα参与基础睡眠和睡眠稳态，而CaMKIIβ在生理上主要是睡眠稳态所必需的，这为未来的深入研究提供了动力。
