PROJECT: JTC2023 - Resilience: KetoResi

In this translational research project involving (i) two rodent models of stress resilience and (ii) existing human cohorts that were previously characterized regarding stress resilience in an ongoing longitudinal study, we will assess the hypothesis that a pharmacological intervention with the ketone body ß-hydroxybutyrate (BHB) is able to promote stress resilience. This hypothesis is substantiated on one hand by the current knowledge on candidate stress resilience mechanisms and, on the other hand, on data showing that ketogenic signaling is able to positively modulate many of the potential resilience mechanisms. Here, we aim at investigating several of these underlying mechanisms and identifying potential molecular and behavioral predictors of stress resilience. In a multidisciplinary approach, this consortium will implement a broad range of state-of-the-art techniques, including behavioral analyses, transcriptomics, epigenetics, metabolic investigations, in vivo imaging in rodents (fMRI, calcium imaging, neurotransmitter sensors) and in humans (fMRI). We explore a promising but poorly understood field in resilience research, e.g., the link between stress resilience and metabolism. The suggested interventions are easily applicable, self-determining, and affordable, and importantly without ethical dilemmas. Thus, in the current times of high load of stress, this project will decisively contribute to improve the general health and to alleviate stress-related disorders.