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Study of the neurobiological basis of trauma in a Dutch military cohort and a mouse model: a unique cross-species perspective
Koper, Marta J.
- Master Thesis
Rights / licenseIn Copyright - Non-Commercial Use Permitted
While the physiological fight-or-flight response to acute stress contributes to the survival advantage in evolutionary terms, a long-lasting exposure to traumatic stress may induce enduring dysfunctions of the body systems. Both early-life and adult trauma lead to the neuroendocrine and epigenetic changes, which are the basis for the development of mental and physiological disorders. A recent Dutch military cohort study has provided evidence on molecular substrates underpinning clinical conditions after combat trauma. Based on these data, a crossspecies analysis was carried out to compare whether biological alterations found in traumatized soldiers overlap with those induced by early-life trauma exposure. For this, a mouse model combining early-life unpredictable maternal separation with unpredictable maternal stress (MSUS) was used, and candidate genes, such as ZFP57 and RNF39, were investigated in terms of mRNA expression and DNA methylation. The human trauma-induced DNA methylation changes were not found in MSUS for these two candidate genes. Serum microRNA profiling revealed aberrant expression of miR-34b, miR-146a, miR-146b and miR- 370 in MSUS mice relative to controls. A subsequent literature analysis of microRNA targets suggested its potential implication in the neuroendocrine, immune and metabolic downstream signalling pathways. Bridging the bench with the bedside, further research in both rodents and humans would benefit from the current findings by continuing the investigation of traumainduced phenotypic changes Show more
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ContributorsSupervisor: Mansuy, Isabelle M.
Supervisor: Rutten, Bart
SubjectmicroRNAs, DNA methylation, gene expression, traumatic stress
Organisational unit03518 - Mansuy, Isabelle
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