Institute for Behavioral Genetics, University of Colorado, Boulder, United States.
Institute for Behavioral Genetics, University of Colorado, Boulder, United States; Department of Integrative Physiology, University of Colorado, Boulder, United States; Linda Crnic Institute, Anschutz Medical School, Denver, CO, United States.
Neuroscience. 2018 Apr 15;376:117-126. doi: 10.1016/j.neuroscience.2018.02.009. Epub 2018 Feb 16.
Down syndrome (DS) results from the triplication of genes located on human chromosome 21 (Hsa21). Though many cognitive and behavioral impairments are associated with DS, sleep disturbances remain poorly understood despite being a reported phenotype in approximately 60% of individuals diagnosed with DS. In this study, sleep and electroencephalography (EEG) oscillations were recorded from aged (12-14 mos.) Dp(16)1Yey/+ mice (Dp16), a mouse model of DS. We observed disrupted sleep demonstrated by increased activity during the dark phase and increased time awake at the expense of NREM sleep compared to wild-type mice. In addition, we found that Dp16 mice display significant differences in relative EEG power distribution among oscillation frequencies in both sleep and awake states. These results in Dp16 mice are consistent with sleep disturbances found in individuals with DS, and the abnormal EEG oscillations in aged Dp16 mice suggest a potential role for GABAergic activity in these sleep and EEG abnormalities. These sleep and EEG data reflect underlying differences in neuronal activity at the network level and thus are causative agents rather than merely symptoms of DS.
唐氏综合征(DS)是由于人类 21 号染色体(Hsa21)上基因的三倍体引起的。尽管许多认知和行为障碍与 DS 有关,但睡眠障碍尽管在大约 60%的 DS 患者中被报道为表型,但仍未得到充分理解。在这项研究中,从年龄较大(12-14 个月)的 Dp(16)1Yey/+ 小鼠(Dp16)中记录了睡眠和脑电图(EEG)振荡,Dp16 是 DS 的一种小鼠模型。我们观察到睡眠受到干扰,表现在与野生型小鼠相比,暗期活动增加,NREM 睡眠时间减少。此外,我们发现 Dp16 小鼠在睡眠和清醒状态下的振荡频率之间的相对 EEG 功率分布存在显著差异。Dp16 小鼠的这些结果与在 DS 个体中发现的睡眠障碍一致,并且在老年 Dp16 小鼠中异常的 EEG 振荡表明 GABA 能活动在这些睡眠和 EEG 异常中可能发挥作用。这些睡眠和 EEG 数据反映了在网络水平上神经元活动的潜在差异,因此是病因,而不仅仅是 DS 的症状。