Department of Pharmacology and Toxicology, Institute of Pharmacy and CMBI, University of Innsbruck, Innsbruck, Austria.
Department of Anesthesiology and Intensive Care, School of Medicine, Klinikum Rechts Der Isar, Technical University of Munich, Ismaninger Straße 22, 81675, Munich, Germany.
Sci Rep. 2021 Apr 26;11(1):8978. doi: 10.1038/s41598-021-88475-2.
Sleep disturbances are a common complaint of anxiety patients and constitute a hallmark feature of post-traumatic stress disorder (PTSD). Emerging evidence suggests that poor sleep is not only a secondary symptom of anxiety- and trauma-related disorders but represents a risk factor in their development, for example by interfering with emotional memory processing. Fear extinction is a critical mechanism for the attenuation of fearful and traumatic memories and multiple studies suggest that healthy sleep is crucial for the formation of extinction memories. However, fear extinction is often impaired in anxiety- and trauma-related disorders-an endophenotype that is perfectly modelled in the 129S1/SvImJ inbred mouse strain. To investigate whether these mice exhibit altered sleep at baseline that could predispose them towards maladaptive fear processing, we compared their circadian sleep/wake patterns to those of typically extinction-competent C57BL/6 mice. We found significant differences regarding diurnal distribution of sleep and wakefulness, but also sleep architecture, spectral features and sleep spindle events. With regard to sleep disturbances reported by anxiety- and PTSD patients, our findings strengthen the 129S1/SvImJ mouse models' face validity and highlight it as a platform to investigate novel, sleep-focused diagnostic and therapeutic strategies. Whether the identified alterations causally contribute to its pathological anxiety/PTSD-like phenotype will, however, have to be addressed in future studies.
睡眠障碍是焦虑症患者常见的主诉，也是创伤后应激障碍（PTSD）的一个显著特征。新出现的证据表明，睡眠质量差不仅是焦虑和与创伤相关障碍的继发症状，而且是其发展的一个风险因素，例如通过干扰情绪记忆处理。恐惧消退是减弱恐惧和创伤记忆的关键机制，多项研究表明，健康的睡眠对于消退记忆的形成至关重要。然而，在焦虑和与创伤相关的障碍中，恐惧消退常常受损，这是一种内表型，在 129S1/SvImJ 近交系小鼠中得到了很好的模拟。为了研究这些小鼠是否在基线时表现出改变的睡眠，从而使它们更容易产生适应不良的恐惧处理，我们将它们的昼夜睡眠/觉醒模式与通常具有良好的消退能力的 C57BL/6 小鼠进行了比较。我们发现，它们在睡眠和觉醒的昼夜分布方面存在显著差异，还包括睡眠结构、光谱特征和睡眠纺锤波事件。关于焦虑症和 PTSD 患者报告的睡眠障碍，我们的发现增强了 129S1/SvImJ 小鼠模型的表面效度，并强调它是一个研究新的、以睡眠为重点的诊断和治疗策略的平台。然而，所确定的改变是否会导致其病理性焦虑/创伤后应激障碍样表型，将需要在未来的研究中解决。
