Constant light housing during nursing causes human DSPS (delayed sleep phase syndrome) behaviour in Clock‐mutant mice

Constant light housing during nursing causes human DSPS (delayed sleep phase syndrome) behaviour in Clock‐mutant mice
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护理期间持续光照的环境会导致时钟突变小鼠出现人类 DSPS(睡眠相位延迟综合征)行为

DOI:
10.1111/j.1460-9568.2007.05490.x
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发表时间:
2007
影响因子:
3.4
通讯作者:
S. Shibata
S. Shibata
中科院分区:
医学3区
文献类型:
--
作者:
Y. Wakatsuki;T. Kudo;S. Shibata

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睡眠相延迟综合征(DSPS)在睡眠-觉醒节律紊乱的患者中非常常见。携带人类时钟基因3111C等位基因的人倾向于在早晨-夜晚偏好测试中表现出更高的夜晚偏好。DSP被认为是这种晚间喜好的一种极端形式。时钟突变小鼠被认为是偏爱夜晚的动物模型。在这项研究中,我们观察了哺乳期间时钟突变小鼠的恒定光照(LL)是否会导致晚上偏好和/或DSPs。在哺乳期,在明暗(LD)或恒暗(DD)条件下,野生型和时钟突变小鼠在明暗条件下测量的运动活动都没有表现出相位延迟,而在哺乳期持续光照显著地导致延迟开始。光-暗周期中延迟的大小与在恒定黑暗中测量的自由运行时间呈正相关。在从杂合子母猪出生的野生、杂合子和纯合子幼崽中,只有纯合子幼崽表现出延迟发病。恒定光照条件下的时钟突变小鼠在视交叉上核(SCN)核心区的磷酸化MAPK免疫反应细胞数量较少,峰值延迟,与光暗环境下野生型或时钟突变小鼠相比。每天在熄灯时注射褪黑素5 后,活动开始恢复正常。目前的结果表明,在哺乳期持续光照下的时钟突变小鼠可以作为dsPS的动物模型,并可以用来了解dsPS的行为学方面,以及寻找治疗该病的药物。
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.
DOI: --
发表时间: 1999-03
期刊: Journal of investigative medicine : the official publication of the American Federation for Clinical Research
影响因子: --
作者:
J. Duffy;D. Dijk;Edward F. Hall;C. Czeisler
通讯作者: J. Duffy;D. Dijk;Edward F. Hall;C. Czeisler
DOI: 10.1126/science.8171325
发表时间: 1994-04-29
期刊: SCIENCE
影响因子: 56.9
作者:
VITATERNA, MH;KING, DP;TAKAHASHI, JS
通讯作者: TAKAHASHI, JS
DOI: 10.1093/sleep/21.6.569
发表时间: 1998-09-15
期刊: SLEEP
影响因子: 5.6
作者:
Katzenberg, D;Young, T;Mignot, E
通讯作者: Mignot, E