Department of Psychology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada.
Hotchkiss Brain Institute, Cummings School of Medicine, University of Calgary, Calgary, AB, Canada.
Sci Rep. 2022 May 5;12(1):7366. doi: 10.1038/s41598-022-11335-0.
Healthy sleep supports robust development of the brain and behavior. Modern society presents a host of challenges that can impair and disrupt critical circadian rhythms that reinforce optimal physiological functioning, including the proper timing and consolidation of sleep. While the acute effects of inadequate sleep and disrupted circadian rhythms are being defined, the adverse developmental consequences of disrupted sleep and circadian rhythms are understudied. Here, we exposed mice to disrupting light-dark cycles from birth until weaning and demonstrate that such exposure has adverse impacts on brain and behavior as adults. Mice that experience early-life circadian disruption exhibit more anxiety-like behavior in the elevated plus maze, poorer spatial memory in the Morris Water Maze, and impaired working memory in a delayed match-to-sample task. Additionally, neuron morphology in the amygdala, hippocampus and prefrontal cortex is adversely impacted. Pyramidal cells in these areas had smaller dendritic fields, and pyramidal cells in the prefrontal cortex and hippocampus also exhibited diminished branching orders. Disrupted mice were also hyperactive as adults, but otherwise exhibited no alteration in adult circadian locomotor rhythms. These results highlight that circadian disruption early in life may have long lasting and far-reaching consequences for the development of behavior and the brain.
健康的睡眠有助于大脑和行为的健康发育。现代社会存在许多挑战,这些挑战会损害和扰乱强化最佳生理功能的关键昼夜节律,包括睡眠的适当时间和巩固。虽然睡眠不足和昼夜节律紊乱的急性影响正在被定义,但睡眠和昼夜节律紊乱的不良发育后果还没有得到充分研究。在这里,我们从出生到断奶期间让老鼠暴露在打乱的明暗周期中,结果表明这种暴露会对成年后的大脑和行为产生不良影响。经历早期生活昼夜节律中断的老鼠在高架十字迷宫中表现出更多的焦虑样行为,在 Morris 水迷宫中的空间记忆更差,在延迟匹配样本任务中的工作记忆受损。此外,杏仁核、海马体和前额叶皮层的神经元形态也受到不利影响。这些区域的锥体神经元的树突场更小,而前额叶皮层和海马体的锥体神经元的分支顺序也减少。被打乱的老鼠在成年后也表现得过度活跃,但在其他方面,成年昼夜节律运动节律没有改变。这些结果表明,生命早期的昼夜节律中断可能对行为和大脑的发育产生持久而深远的影响。