Biosignal Research Center, Kobe University, Kobe, Hyogo, Japan; Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo, Japan.
Healthy Food Science Research Group, Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
Biochem Biophys Res Commun. 2020 Aug 20;529(2):175-179. doi: 10.1016/j.bbrc.2020.05.218. Epub 2020 Jun 22.
Sleep disturbances can contribute to cognitive decline and neuropsychiatric disorders. However, the underlying mechanisms of these processes are poorly understood. The present study evaluated the effects of a chronic sleep disorder (CSD) on long-term memory formation and anxiety-like behavior in our originally established mouse model of psychophysiological stress-induced CSD characterized by disrupted circadian rhythms of wheel-running activity and sleep-wake cycles. Model mice are continuously exposed to mild stress imposed by perpetually staying on a running-wheel to avoid water. The findings of novel object recognition (NORT) and open field (OFT) tests showed that CSD impaired recognition memory and elicited anxiety-like behavior, respectively. These results suggested that the CSD impaired cognitive function and emotional status. Thus, this CSD model could be useful for studying the underlying mechanisms of neurobehavioral difficulties caused by sleep disorders. We then examined the hippocampal mRNA expression of genes associated with learning and memory, and anxiety and depression. The CSD increased the mRNA expression of Crhr1, Ngf and Phlpp1, and suppressed that of Ace, Egr2 and Slc6a4. Based on the functions of these genes, we inferred that the increase in Crhr1 mRNA was associated with the pathogenesis of psychiatric conditions, whereas mRNA levels of the other five genes were directed towards symptom relief. Upregulating hippocampal Crhr1 expression might contribute in part to the activation of corticotropin-releasing hormone (CRH)-CRH receptor1 signaling that mediates CSD-evoked mental disorders.
睡眠障碍可导致认知能力下降和神经精神疾病。然而，这些过程的潜在机制尚不清楚。本研究评估了慢性睡眠障碍（CSD）对我们最初建立的心理生理性应激诱导 CSD 小鼠模型中长时记忆形成和焦虑样行为的影响，该模型的特征是轮跑活动和睡眠-觉醒周期的昼夜节律紊乱。模型小鼠持续暴露于通过持续在跑步轮上避免水施加的轻度应激下。新颖物体识别（NORT）和旷场（OFT）测试的结果表明，CSD 分别损害了识别记忆并引起了焦虑样行为。这些结果表明，CSD 损害了认知功能和情绪状态。因此，这种 CSD 模型可用于研究由睡眠障碍引起的神经行为困难的潜在机制。然后，我们检查了与学习和记忆以及焦虑和抑郁相关的海马体 mRNA 表达。CSD 增加了 Crhr1、Ngf 和 Phlpp1 的 mRNA 表达，而抑制了 Ace、Egr2 和 Slc6a4 的表达。基于这些基因的功能，我们推断 Crhr1 mRNA 的增加与精神疾病的发病机制有关，而其他五个基因的 mRNA 水平则指向症状缓解。上调海马体 Crhr1 的表达可能部分有助于介导 CSD 诱发的精神障碍的促肾上腺皮质激素释放激素（CRH）-CRH 受体 1 信号转导的激活。
