PDF(Pubmed)
Abstract：
Prior research has identified differential protein expression levels of linker histone H1x within the ventral hippocampus (vHipp) of stress-susceptible versus stress-resilient mice. These mice are behaviorally classified based on their divergent responses to chronic social stress. Here, we sought to determine whether elevated vHipp H1x protein levels directly contribute to these diverging behavioral adaptations to stress. First, we demonstrated that stress-susceptible mice uniquely express elevated vHipp H1x protein levels following chronic stress. Given that linker histones coordinate heterochromatin compaction, we hypothesize that elevated levels of H1x in the vHipp may impede pro-resilience transcriptional adaptations and prevent development of the resilient phenotype following social stress. To test this, 8-10-week-old male C57BL/6 J mice were randomly assigned to groups undergoing 10 days of chronic social defeat stress (CSDS) or single housing, respectively. Following CSDS, mice were classified as susceptible versus resilient based on their social interaction behaviors. We synthesized a viral overexpression (OE) vector for H1x and transduced all stressed and single housed mice with either H1x or control GFP within vHipp. Following viral delivery, we conducted social, anxiety-like, and memory-reliant behavior tests on distinct cohorts of mice. We found no behavioral adaptations following H1x OE compared to GFP controls in susceptible, resilient, or single housed mice. In sum, although we confirm elevated vHipp protein levels of H1x associate with susceptibility to social stress, we observe no significant behavioral consequence of H1x OE. Thus, we conclude elevated levels of H1x are associated with, but are not singularly sufficient to drive development of behavioral adaptations to stress.
摘要：
先前的研究已经确定了应激易感与应激弹性小鼠的腹侧海马（vHipp）中接头组蛋白H1x的差异蛋白质表达水平。这些小鼠根据其对慢性社会压力的不同反应进行行为分类。这里,我们试图确定升高的vHippH1x蛋白水平是否直接导致这些不同的行为适应应激.首先,我们证明了应激易感小鼠在慢性应激后独特表达升高的vHippH1x蛋白水平.鉴于接头组蛋白协调异染色质压缩，我们假设,在vHipp中升高的H1x水平可能会阻碍亲复原力转录适应,并阻止社会压力后复原力表型的发展.为了测试这个，将8-10周龄的雄性C57BL/6J小鼠随机分配到经历10天慢性社会失败应激（CSDS）或单一住房的组，分别。在CSDS之后，根据小鼠的社交互动行为，将小鼠分为易感和弹性。我们合成了用于H1x的病毒过表达（OE）载体，并在vHipp中用H1x或对照GFP转导了所有应激和单饲养小鼠。病毒递送后，我们进行社交，像焦虑一样，和对不同队列小鼠的记忆相关行为测试。与易感基因的GFP对照相比，我们发现在H1xOE后没有行为适应，弹性，或单一饲养的老鼠。总之,虽然我们证实了h1x的vhipp蛋白水平升高与社会压力的易感性有关，我们没有观察到H1xOE的显著行为后果。因此，我们得出的结论是，H1N1x水平升高与，但并不足以推动对压力的行为适应发展。
