Long-term molecular differences between resilient and susceptible mice after a single traumatic exposure.
BACKGROUND AND PURPOSE
PTSD is a heterogeneous disorder induced by trauma, resulting in severe long-term impairments of an individual's mental health. Interestingly, PTSD does not develop in every individual; thus, some individuals are more resilient than others. However, the underlying molecular mechanisms are poorly understood. Here, we aimed at shedding light on these processes.


EXPERIMENTAL APPROACH
We used a single-trauma PTSD model in mice to induce long-term maladaptive behaviours and profiled the mice four weeks post-trauma into resilient or susceptible individuals. The phenotype's classification was based on their 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 a plethora of molecular differences between resilient and susceptible individuals across multiple molecular domains, including lipidome, transcriptome, and gut microbiome. Some of these 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 multi-layered molecular data revealed that resilient and susceptible individuals have very distinct molecular signatures across various physiological systems.


CONCLUSIONS AND IMPLICATIONS
We showed that trauma induces individual-specific behavioural responses that, in combination with a longitudinal characterization of mice, can be used to identify distinct sub-phenotypes within the trauma-exposed group. These groups differ 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.
['Pascual Cuadrado|Diego|D|https://orcid.org/0000-0002-6170-4330', 'Todorov|Hristo|H|', 'Lerner|Raissa|R|', 'Islami|Larglinda|L|', 'Bindila|Laura|L|', 'Gerber|Susanne|S|', 'Lutz|Beat|B|']
resilience trauma microbiome endocannabinoids lipidomics behavioural profiling