Profitt Maxine F, Deurveilher Samuel, Robertson George S, Rusak Benjamin, Semba Kazue
Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada;
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada; Department of Pharmacology, Dalhousie University, Halifax, NS, Canada;
Schizophr Bull. 2016 Sep;42(5):1207-15. doi: 10.1093/schbul/sbw017. Epub 2016 Mar 2.
Disruption of sleep/wake cycles is common in patients with schizophrenia and correlates with cognitive and affective abnormalities. Mice deficient in stable tubule only polypeptide (STOP) show cognitive, behavioral, and neurobiological deficits that resemble those seen in patients with schizophrenia, but little is known about their sleep phenotype. We characterized baseline sleep/wake patterns and recovery sleep following sleep deprivation in STOP null mice. Polysomnography was conducted in adult male STOP null and wild-type (WT) mice under a 12:12 hours light:dark cycle before, during, and after 6 hours of sleep deprivation during the light phase. At baseline, STOP null mice spent more time awake and less time in non-rapid eye movement sleep (NREMS) over a 24-hour period, with more frequent transitions between wake and NREMS, compared to WT mice, especially during the dark phase. The distributions of wake, NREMS and REMS across the light and the dark phases differed by genotype, and so did features of the electroencephalogram (EEG). Following sleep deprivation, both genotypes showed homeostatic increases in sleep duration, with no significant genotype differences in the initial compensatory increase in sleep intensity (EEG delta power). These results indicate that STOP null mice sleep less overall, and their sleep and wake periods are more fragmented than those of WT mice. These features in STOP null mice are consistent with the sleep patterns observed in patients with schizophrenia.
睡眠/觉醒周期紊乱在精神分裂症患者中很常见,且与认知和情感异常相关。缺乏稳定微管专一多肽(STOP)的小鼠表现出与精神分裂症患者相似的认知、行为和神经生物学缺陷,但对其睡眠表型知之甚少。我们对STOP基因敲除小鼠的基线睡眠/觉醒模式以及睡眠剥夺后的恢复睡眠进行了特征描述。在光照期进行6小时睡眠剥夺之前、期间和之后,对成年雄性STOP基因敲除小鼠和野生型(WT)小鼠在12:12小时光照:黑暗周期下进行多导睡眠图监测。在基线时,与WT小鼠相比,STOP基因敲除小鼠在24小时内清醒时间更长,非快速眼动睡眠(NREMS)时间更短,在清醒和NREMS之间的转换更频繁,尤其是在黑暗期。觉醒、NREMS和快速眼动睡眠(REMS)在光照期和黑暗期的分布因基因型而异,脑电图(EEG)特征也是如此。睡眠剥夺后,两种基因型的睡眠时长均出现稳态增加,在睡眠强度的初始代偿性增加(EEGδ功率)方面没有显著的基因型差异。这些结果表明,STOP基因敲除小鼠总体睡眠时间较少,其睡眠和觉醒周期比WT小鼠更碎片化。STOP基因敲除小鼠的这些特征与精神分裂症患者观察到的睡眠模式一致。