While post-traumatic stress disorder (PTSD) is defined by behavioral/cognitive symptoms most directly relevant to brain function, it can be considered a systemic disorder characterized by a distinct inability to reinstate homeostasis after trauma. In this study, we conducted a secondary analysis of gene expression profiles in key PTSD-relevant tissues, namely blood, amygdala, and hippocampus, from a rat model of PTSD, to identify sex-specific and shared processes associated with individual differences in response to recent trauma exposure. Our findings suggest both shared and sex-specific mechanisms underlying individual differences associated with vulnerability and resilience to trauma in hippocampus, amygdala, and blood. By disentangling cell composition from transcriptional changes, we found higher proportions of hippocampal oligodendrocytes in the PTSD-like, extreme behavioral response (EBR) group for both sexes and also identified modules for transcriptional activity associated with group differences (i.e., response to trauma) in the hippocampus that appeared to be sex-specific. By contrast, we found prominent sex differences, but no group differences, in amygdalar cell composition, and both shared and sex-specific modules representing PTSD-relevant transcriptional activity in the amygdala. Across amygdala and hippocampus, both sex-specific and shared processes were relevant to an overarching framework for EBR implicating disrupted TNFα/NFκΒ signaling and excitatory/inhibitory imbalance in dysregulated synaptic/structural plasticity with important implications for fear learning and memory. Our main finding in peripheral blood was consistent with the human literature and identified wound healing processes and hemostasis to be upregulated in the resilient, minimal behavioral response (MBR) group across sexes, but disrupted in a sexually dimorphic manner in the EBR group. In contrast to the varied characterization of the PTSD-like EBR group, characterization of MBR across blood, amygdala, and hippocampus suggests a common theme of upregulated wound healing and extracellular matrix (ECM) remodeling shared between sexes. In all, we identified differential oligodendrocyte proportions in hippocampus between PTSD-like EBR and resilient MBR, and identified processes and pathways that characterize the EBR and MBR-associated transcriptional changes across hippocampus, amygdala, and blood. The sex-specific mechanisms involved in EBR may contribute to the pronounced disparity in risk for PTSD, with women much more likely to develop PTSD.

中文翻译：

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大脑和血液中对创伤的脆弱性和复原力的性别特定且共享的表达方式。

创伤后应激障碍（PTSD）是由与脑功能最直接相关的行为/认知症状定义的，但可以将其视为以创伤后无法恢复稳态为特征的系统性疾病。在这项研究中，我们对PTSD的大鼠模型中与PTSD相关的关键组织（即血液，杏仁核和海马体）的基因表达谱进行了二次分析，以鉴定与个体差异相关的性别特异性和共有过程最近的创伤暴露。我们的研究结果表明，共有的和特定性别的机制都潜在于个体差异，这些差异与海马，杏仁核和血液的脆弱性和对创伤的抵抗力有关。通过区分细胞组成与转录变化，我们发现PTSD样，极端行为反应（EBR）组中的男女海马少突胶质细胞比例都较高，并且还发现了与似乎是性别的海马体中的群体差异（即对创伤的反应）相关的转录活性模块。具体。相比之下，我们发现杏仁核细胞组成中存在明显的性别差异，但没有群体差异，并且在杏仁核中代表PTSD相关转录活性的共享模块和性别特定模块。在整个杏仁核和海马体中，性别特异性过程和共享过程都与EBR的总体框架有关，该框架涉及破坏的突触/结构可塑性中破坏的TNFα/NFκB信号传导和兴奋性/抑制性不平衡，对恐惧学习和记忆具有重要意义。我们在外周血中的主要发现与人类文献一致，并且发现伤口的愈合过程和止血在两性之间的弹性，最小行为反应（MBR）组中被上调，但在EBR组中以性二态性破坏。与类似PTSD的EBR组的特征不同，跨血，杏仁核和海马体的MBR的特征表明，男女之间共有一个上调伤口愈合和细胞外基质（ECM）重塑的共同主题。总之，我们确定了PTSD样EBR和弹性MBR之间海马中少突胶质细胞的比例，并确定了表征EBR和MBR相关的海马，杏仁核和血液转录变化的过程和途径。