Abstract

Social defeat stress affects behavior and changes the expression of the genes underlying neuronal plasticity in the brain. The circadian clock regulates most neuronal processes in the brain, which results in daily variations of complex behavior, and any disturbance in circadian clock oscillations increases the risk of mood and cognitive disbalance. In this study, we assessed the effect of acute and repeated social defeat stress on Per2 and Nr1d1 expression in prefrontal cortexes, hippocampi, pineal glands, olfactory bulbs, cerebella, and pituitary glands. We also evaluated the effect of our experimental setting on levels of Bdnf and plasma corticosterone, two markers widely used to asses the impact of stress on mammalian physiology. Our data show that single and repeated social defeat stress upregulates the expression of both clock genes and Bdnf in all brain structures, and corticosterone in the blood. While the general pattern of Bdnf upregulation suggests higher sensitivity in the intruder group, the clock genes are induced more significantly in residents, especially by repeated stress sessions. Our work thus suggests that the model of stress-induced anxiety and depression should consider a group of residents because, for some parameters, they may respond more distinctively than intruders.

• LAY SUMMARY

• The resident/intruder experimental paradigm affects the expression of clock genes Per2, Nr1d1and Bdnf in the brain structures and plasma corticosterone level. The induction of clock genes is evident in both experimental groups; however, it is more marked in residents. Together with the significant increase in Bdnf levels in the majority of brain structures and plasma corticosterone in residents, our data suggest that in the model of social defeat stress, the utility of an experimental group of residents could be contributive.

摘要

社会挫败压力会影响行为并改变大脑神经元可塑性背后的基因表达。昼夜节律时钟调节大脑中的大多数神经元过程，从而导致复杂行为的日常变化，并且昼夜节律时钟振荡的任何紊乱都会增加情绪和认知失衡的风险。在这项研究中，我们评估了急性和反复社交挫败压力对前额叶皮层，海马，松果体，嗅球，小脑和垂体中Per2和Nr1d1表达的影响。我们还评估了实验环境对Bdnf水平的影响和血浆皮质酮，这两个标记物被广泛用于评估压力对哺乳动物生理的影响。我们的数据表明，一次和多次社交失败压力会上调所有大脑结构中时钟基因和Bdnf的表达，同时还会上调血液中的皮质酮的表达。虽然Bdnf上调的一般模式表明入侵者组的敏感性更高，但居民中时钟基因的诱导更为显着，特别是反复出现的应激阶段。因此，我们的工作表明，压力引起的焦虑和抑郁模型应考虑一组居民，因为在某些参数上，他们的反应可能比入侵者更具特色。

• 图层摘要

• 驻留/入侵者实验范式影响大脑结构和血浆皮质酮水平中时钟基因Per2，Nr1d1和Bdnf的表达。时钟基因的诱导在两个实验组中都是明显的。但是，它在居民中更为明显。我们的数据表明，在居民大多数大脑结构和血浆皮质酮的Bdnf水平显着增加的情况下，在社交挫败压力模型中，实验组居民的效用可能是有贡献的。