Prader–Willi syndrome (PWS) is a neurodevelopmental disorder that is characterized by metabolic alteration and sleep abnormalities mostly related to rapid eye movement (REM) sleep disturbances. The disease is caused by genomic imprinting defects that are inherited through the paternal line. Among the genes located in the PWS region on chromosome 15 (15q11-q13), small nucleolar RNA 116 (Snord116) has been previously associated with intrusions of REM sleep into wakefulness in humans and mice. Here, we further explore sleep regulation of PWS by reporting a study with PWScr^m+/p− mouse line, which carries a paternal deletion of Snord116. We focused our study on both macrostructural electrophysiological components of sleep, distributed among REMs and nonrapid eye movements. Of note, here, we study a novel electroencephalography (EEG) graphoelements of sleep for mouse studies, the well-known spindles. EEG biomarkers are often linked to the functional properties of cortical neurons and can be instrumental in translational studies. Thus, to better understand specific properties, we isolated and characterized the intrinsic activity of cortical neurons using in vitro microelectrode array. Our results confirm that the loss of Snord116 gene in mice influences specific properties of REM sleep, such as theta rhythms and, for the first time, the organization of REM episodes throughout sleep–wake cycles. Moreover, the analysis of sleep spindles present novel specific phenotype in PWS mice, indicating that a new catalog of sleep biomarkers can be informative in preclinical studies of PWS.

中文翻译：

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Snord116 的缺失改变了小鼠的皮质神经元活动：Prader-Willi 综合征的临床前研究。

Prader-Willi 综合征 (PWS) 是一种神经发育障碍，其特征是代谢改变和睡眠异常，主要与快速眼动 (REM) 睡眠障碍有关。这种疾病是由通过父系遗传的基因组印记缺陷引起的。在位于 15 号染色体 (15q11-q13) 上 PWS 区域的基因中，小核仁 RNA 116 ( Snord116 ) 以前曾与 REM 睡眠侵入人类和小鼠的清醒状态有关。在这里，我们通过报告一项关于 PWScr ^m+/p−小鼠品系的研究，进一步探索了 PWS 的睡眠调节，该品系携带Snord116的父本缺失。我们将研究重点放在睡眠的宏观结构电生理成分上，分布在 REM 和非快速眼球运动中。值得注意的是，在这里，我们研究了一种用于小鼠研究的新型脑电图 (EEG) 睡眠图元，即众所周知的纺锤体。EEG 生物标志物通常与皮层神经元的功能特性有关，并且可以在转化研究中发挥作用。因此，为了更好地了解特定特性，我们使用体外微电极阵列分离并表征了皮层神经元的内在活动。我们的结果证实了Snord116的损失小鼠中的基因影响 REM 睡眠的特定特性，例如 theta 节律，以及首次在整个睡眠 - 觉醒周期中组织 REM 发作。此外，对睡眠纺锤波的分析在 PWS 小鼠中呈现出新的特定表型，表明新的睡眠生物标志物目录可为 PWS 的临床前研究提供信息。