Bartlang Manuela S, Oster Henrik, Helfrich-Förster Charlotte
University of Würzburg, Biocenter, Theodor-Boveri-Institute, Neurobiology and Genetics, Würzburg, Germany.
University of Lübeck, Chronophysiology Group, Medical Department 1, Lübeck, Germany.
J Biol Rhythms. 2015 Jun;30(3):228-41. doi: 10.1177/0748730415576192. Epub 2015 Apr 20.
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.
我们最近发现，在黑暗/活跃期（社会挫败黑暗期[SDD]）重复遭受社会挫败（SD）会影响小鼠视交叉上核（SCN）中的分子节律，而在光照/不活跃期（社会挫败光照期[SDL]）重复遭受SD对SCN中PERIOD2::荧光素酶外植体节律没有影响。在此，我们通过体内生物遥测技术评估了相同应激模式对野生型（WT）和生物钟缺陷型Period（Per）1/2双突变小鼠在重复SDL和SDD期间及之后的昼夜节律钟的两个输出节律（即活动和核心体温）的影响。一般来说，与体温节律相比，应激对活动的影响更为明显。在整个SD过程中，在生物钟时间（ZT）1至ZT3（SDL小鼠）和ZT13至ZT15（SDD小鼠）的2小时应激源暴露期间，活动和体温显著升高，这在两种基因型的小鼠中，通过剩余黑暗期（SDL和SDD小鼠）和光照期（SDL小鼠）活动的减少得到了补偿。在应激后时期，SDL和SDD小鼠的活动存在显著差异。与单笼饲养对照（SHC）和SDL小鼠相比，SDD小鼠在ZT13的首次活动发作减少，活动开始延迟，因此活动带宽更窄。鉴于这种效应在Per1/2突变的SDD小鼠中不存在，并且在SDD野生型小鼠的持续黑暗条件下持续存在，这表明内源性生物钟参与其中。综上所述，目前的研究结果表明，SDD对生物钟的功能输出具有长期影响，至少部分似乎依赖于生物钟基因Per1和Per2。
