Wakatsuki Yukako, Kudo Takashi, Shibata Shigenobu
Department of Physiology and Pharmacology, School of Science and Engineering, Waseda University, Higashifushimi 2-7-5, Nishitokyo, 202-0021 Japan.
Eur J Neurosci. 2007 Apr;25(8):2413-24. doi: 10.1111/j.1460-9568.2007.05490.x.
Delayed sleep phase syndrome (DSPS) is very often seen among patients with sleep-wake rhythm disorders. Humans with the 3111C allele of the human Clock gene tend to demonstrate a higher evening preference on the morningness-eveningness (ME) preference test. DSPS is thought to be an extreme form of this evening preference. Clock-mutant mice have been proposed as an animal model of evening preference. In this study, we looked at whether constant light (LL) housing of Clock-mutant mice during lactation would result in evening preference and/or DSPS. Housed under light-dark (LD) or constant dark (DD) conditions during the lactation period, both wild-type and Clock-mutant mice did not show a phase-delay in the locomotor activity measured under light-dark conditions, whereas constant light housing during lactation significantly caused a delayed onset. The magnitude of the delay during the light-dark cycle was positively associated with free-running period measured during constant darkness. Among wild, heterozygote, and homozygote pups born from heterozygous dams, only homozygote pups showed a delayed onset. Constant light-housed Clock-mutant mice exhibited a lower number and delayed peak of phospho-MAPK-immunoreactive cells in core regions of the suprachiasmatic nucleus (SCN) compared to light-dark housed wild-type or Clock-mutant mice. Activity onset returned to normal with daily melatonin injection at the lights-off time for 5 days. The present results demonstrate that Clock-mutant mice exposed to constant light during lactation can function as an animal model of DSPS and can be used to gain an understanding of the ethological aspects of DSPS as well as to find medication for its treatment.
睡眠时相延迟综合征（DSPS）在睡眠-觉醒节律障碍患者中很常见。携带人类生物钟基因3111C等位基因的人在晨型-夜型（ME）偏好测试中往往表现出更高的夜型偏好。DSPS被认为是这种夜型偏好的极端形式。生物钟突变小鼠已被提议作为夜型偏好的动物模型。在本研究中，我们研究了哺乳期的生物钟突变小鼠持续光照（LL）饲养是否会导致夜型偏好和/或DSPS。在哺乳期置于明暗（LD）或持续黑暗（DD）条件下饲养时，野生型和生物钟突变小鼠在明暗条件下测量的运动活动均未出现相位延迟，而哺乳期持续光照饲养则显著导致活动起始延迟。明暗周期中的延迟幅度与持续黑暗期间测量的自由运行周期呈正相关。在杂合子母鼠所生的野生型、杂合子和纯合子幼崽中，只有纯合子幼崽出现活动起始延迟。与明暗饲养的野生型或生物钟突变小鼠相比，持续光照饲养的生物钟突变小鼠视交叉上核（SCN）核心区域中磷酸化丝裂原活化蛋白激酶免疫反应性细胞的数量减少且峰值延迟。在熄灯时间每天注射褪黑素5天可使活动起始恢复正常。目前的结果表明，哺乳期暴露于持续光照的生物钟突变小鼠可作为DSPS的动物模型，可用于了解DSPS的行为学方面以及寻找其治疗药物。
