ABSTRACT

Social jetlag (SJL) is defined as the discrepancy between social and biological rhythms and calculated by the difference between the midpoint of sleep time on working-days and free-days. Previous human and mouse studies showed SJL is positively related to evening chronotype and significantly related to smoking habit, cardiovascular risk, cognitive ability, and that SJL-mimicking conditions, simulating the real lifestyle situation of SJL in many humans, disrupt the regularity of estrous cycles of female animals. The effects of SJL-mimicking conditions on circadian rhythms and cognitive function and the reasons why the discrepancy between social and biological rhythms is involved in SJL have not yet been investigated. Therefore, in this study, we utilized a mouse model of SJL-mimicking conditions – 6-hour delayed-light/dark (LD) conditions for 2 days and normal-LD conditions for the following 5 days – applied for several weeks during which biological rhythms were monitored. Circadian rhythms of central and peripheral clocks and metabolism of the mice under the SJL-mimicking condition were always delayed for 2–3 hours compared with those under the normal-LD condition. Moreover, SJL-mimicking conditions impaired their cognitive function using a novel object recognition test. Only the delayed timing of either the light phase of the LD or of feeding for 2 days, comparable to the free-days situation of humans, delayed the circadian staging of rhythms the following 5 days. Furthermore, sleep deprivation during the early mornings for 5 days, which is comparable to early rise times experienced by humans on working-days and does affect the staging of circadian rhythms (circadian misalignment schedule), delayed the locomotor activity rhythms the next 2 days, comparable to free-days in humans, which is similar to the lifestyle rhythm of the evening chronotype. Our results demonstrated that the circadian misalignment schedule for 5 days changed the locomotor activity rhythms the following 2 days to the evening chronotype, that light- and/or feeding-shift conditions for 2 days exacerbate SJL, and that SJL-mimicking conditions delay the metabolic rhythm and cause cognitive impairment.

摘要

社交时差 (SJL) 被定义为社交和生物节律之间的差异，并通过工作日和空闲日的睡眠时间中点之间的差异计算。先前的人类和小鼠研究表明，SJL 与晚间睡眠类型呈正相关，并与吸烟习惯、心血管风险、认知能力显着相关，并且模拟 SJL 的条件，在许多人中模拟 SJL 的真实生活方式情况，扰乱了发情周期的规律性的雌性动物。SJL 模拟条件对昼夜节律和认知功能的影响以及 SJL 中涉及社会节律和生物节律之间差异的原因尚未得到研究。因此，在本研究中，我们使用模拟 SJL 条件的小鼠模型——2 天的 6 小时延迟光/暗 (LD) 条件和接下来的 5 天的正常 LD 条件——应用数周，在此期间监测生物节律。与正常LD条件下相比，模拟SJL条件下小鼠的中枢和外周时钟和新陈代谢的昼夜节律总是延迟2-3小时。此外，SJL 模拟条件使用新的物体识别测试损害了他们的认知功能。与人类的自由日情况相比，只有 LD 的轻度阶段或喂养 2 天的延迟时间，才延迟了接下来 5 天的昼夜节律分期。此外，在清晨剥夺睡眠 5 天，这与人类在工作日经历的早起时间相当，确实影响昼夜节律的分期（昼夜节律错位时间表），在接下来的 2 天延迟了运动活动节律，与人类的自由日相媲美，类似于晚间型的生活方式节奏。我们的结果表明，5 天的昼夜节律失调计划将接下来 2 天的运动活动节律改变为晚上的睡眠时间型，2 天的光照和/或喂食转移条件会加剧 SJL，而 SJL 模拟条件会延迟代谢节律并导致认知障碍。这与晚间型的生活方式节奏相似。我们的结果表明，5 天的昼夜节律失调计划将接下来 2 天的运动活动节律改变为晚上的睡眠时间型，2 天的光照和/或喂食转移条件会加剧 SJL，而 SJL 模拟条件会延迟代谢节律并导致认知障碍。这与晚间型的生活方式节奏相似。我们的结果表明，5 天的昼夜节律失调计划将接下来 2 天的运动活动节律改变为晚上的睡眠时间型，2 天的光照和/或喂食转换条件会加剧 SJL，而 SJL 模拟条件会延迟代谢节律并导致认知障碍。