Autoren:	Pascual Cuadrado, Diego Todorov, Hristo Lerner, Raissa Islami, Larglinda Bindila, Laura Gerber, Susanne Lutz, Beat
Titel:	Long-term molecular differences between resilient and susceptible mice after a single traumatic exposure
Online-Publikationsdatum:	6-Sep-2022
Erscheinungsdatum:	2022
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	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.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7684
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY-NC
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by-nc/4.0/
Zeitschrift:	British journal of pharmacology 179 17
Seitenzahl oder Artikelnummer:	4161 4180
Verlag:	Wiley
Verlagsort:	Malden, MA
Erscheinungsdatum:	2022
ISSN:	1476-5381
DOI der Originalveröffentlichung:	10.1111/bph.15697
Enthalten in den Sammlungen:	JGU-Publikationen