Long-term molecular differences between resilient and susceptible mice after a single traumatic exposure
Long-term molecular differences between resilient and susceptible mice after a single traumatic exposure
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DOI：
10.1111/bph.15697
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发表时间：
2022-02-15
影响因子：
7.3
通讯作者：
Lutz, Beat
中科院分区：
文献类型：
--
作者：
Cuadrado, Diego Pascual;Todorov, Hristo;Lutz, Beat
背景和目的：创伤后应激障碍（PTSD）是一种由创伤引起的异质性障碍，导致个体心理健康的严重长期损害。创伤后应激障碍不会在每个人身上发展，因此，有些人更有弹性。然而，对潜在的分子机制知之甚少。在这里，我们的目的是阐明这些processes.Experimental方法：我们使用了一个单一的创伤创伤后应激障碍模型在小鼠中诱导长期适应不良行为，并分析了小鼠创伤后4周的弹性或易感个体。表型的分类是基于不同行为实验中的个体反应。我们分析了微生物组，循环内源性大麻素，以及脑磷脂和转录水平的长期变化。关键结果：我们发现弹性和易感个体之间在多个分子结构域，包括脂质组，转录组和肠道微生物组之间存在许多分子差异。一些差异甚至在创伤后几周内保持稳定，表明创伤刺激对生物体生理的长期影响。此外，这些多层的分子数据的整合显示，弹性和易感的个人有非常不同的分子签名在各种生理system.Conclusion和影响：创伤诱导的个人特定的行为反应，结合纵向表征的小鼠，可用于识别不同的亚表型内的创伤暴露组。这些群体不仅在行为上存在显著差异，而且在各种组织和大脑区域的特定分子方面也存在显著差异。这种方法可能揭示新的目标和预测生物标志物的药物治疗和预后的压力相关疾病。
Background and Purpose: Post-traumatic stress disorder (PTSD) is a heterogeneous disorder induced by trauma, resulting in severe long-term impairments of an individual's mental health. PTSD does not develop in every individual and, thus, some individuals are more resilient. However, the underlying molecular mechanisms are poorly understood. Here, we aimed to elucidate these processes.Experimental Approach: We used a single-trauma PTSD model in mice to induce long-term maladaptive behaviours and profiled the mice 4 weeks after trauma into resilient or susceptible individuals. The classification of phenotype was based on individual responses in different behavioural experiments. We analysed microbiome, circulating endocannabinoids, and long-term changes in brain phospholipid and transcript levels.Key Results: We found many molecular differences between resilient and susceptible individuals across multiple molecular domains, including lipidome, transcriptome and gut microbiome. Some differences were stable even several weeks after the trauma, indicating the long-term impact of traumatic stimuli on the organism's physiology. Furthermore, the integration of these multilayered molecular data revealed that resilient and susceptible individuals have very distinct molecular signatures across various physiological systems.Conclusion and Implications: Trauma induced individual-specific behavioural responses that, in combination with a longitudinal characterisation of mice, could be used to identify distinct sub-phenotypes within the trauma-exposed group. These groups differed significantly not only in their behaviour but also in specific molecular aspects across a variety of tissues and brain regions. This approach may reveal new targets and predictive biomarkers for the pharmacological treatment and prognosis of stress-related disorders.