Repeated Psychosocial Stress at Night Affects the Circadian Activity Rhythm of Male Mice

Repeated Psychosocial Stress at Night Affects the Circadian Activity Rhythm of Male Mice
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DOI:
10.1177/0748730415576192
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发表时间:
2015-06-01
影响因子:
3.5
通讯作者:
Helfrich-Foerster, Charlotte
Helfrich-Foerster, Charlotte
中科院分区:
生物学3区
文献类型:
--
作者:
Bartlang, Manuela S.;Oster, Henrik;Helfrich-Foerster, Charlotte

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我们最近的研究表明,小鼠视交叉上核(SCN)的分子节律受到黑暗/活跃阶段(social defeat dark [SDD])的重复社会失败(SD)的影响,而在光明/不活跃阶段(social defeat light [SDL])的重复社会失败(SD)对SCN的PERIOD2::LUCIFERASE外排节律没有影响。在这里,我们通过体内生物遥测技术评估了相同的应激模式对野生型(WT)和时钟缺陷期(Per)1/2双突变小鼠在重复SDL和SDD期间和之后的生物钟2个输出节律(即活动和核心体温)的影响。总的来说,与体温节律相比,压力对活动的影响更为明显。在整个SD过程中,在zeitgeber时间(ZT) 1至ZT3 (SDL小鼠)和ZT13至ZT15 (SDD小鼠),应激源暴露的2小时内,两种基因型小鼠的活性和体温都显著升高,而在剩余的暗期(SDL和SDD小鼠)和光照期(SDL小鼠),活性下降得到了补偿。在应激后时期,SDL和SDD小鼠的活动有相当大的差异。与单房对照(SHC)和SDL小鼠相比,SDD小鼠在ZT13时的第一次活动减少,活动开始延迟,因此活动带宽更窄。鉴于这种影响在Per1/2突变型SDD小鼠中不存在,而在SDD WT小鼠中持续黑暗条件下持续存在,这表明内源性时钟参与其中。综上所述,目前的研究结果表明,SDD对生物钟的功能输出有长期的影响,至少部分地取决于生物钟基因Per1和Per2。
We have recently shown that molecular rhythms in the murine suprachiasmatic nucleus (SCN) are affected by repeated social defeat (SD) during the dark/active phase (social defeat dark [SDD]), while repeated SD during the light/inactive phase (social defeat light [SDL]) had no influence on PERIOD2::LUCIFERASE explant rhythms in the SCN. Here we assessed the effects of the same stress paradigm by in vivo biotelemetry on 2 output rhythms of the circadian clock (i.e., activity and core body temperature) in wild-type (WT) and clock-deficient Period (Per)1/2 double-mutant mice during and following repeated SDL and SDD. In general, stress had more pronounced effects on activity compared to body temperature rhythms. Throughout the SD procedure, activity and body temperature were markedly increased during the 2 h of stressor exposure at zeitgeber time (ZT) 1 to ZT3 (SDL mice) and ZT13 to ZT15 (SDD mice), which was compensated by decreased activity during the remaining dark phase (SDL and SDD mice) and light phase (SDL mice) in both genotypes. Considerable differences in the activity between SDL and SDD mice were seen in the poststress period. SDD mice exhibited a reduced first activity bout at ZT13, delayed activity onset, and, consequently, a more narrow activity bandwidth compared with single-housed control (SHC) and SDL mice. Given that this effect was absent in Per1/2 mutant SDD mice and persisted under constant darkness conditions in SDD WT mice, it suggests an involvement of the endogenous clock. Taken together, the present findings demonstrate that SDD has long-lasting consequences for the functional output of the biological clock that, at least in part, appear to depend on the clock genes Per1 and Per2.