Prof. Dr. David Slattery

This translational project investigates sex-dependent behavioral effects of faecal microbiota transplantation to microbiome-depleted mice from AMD patients (selected based on their aggressive and impulsive traits from Q01), as well as healthy controls. Impulsivity will be assessed via the continuous performance test and responses towards acute threat via the escalated resident intruder test. The goal is to determine the sex-dependent effects of faecal transplantation on selected readouts involved in the transfer of the patient’s phenotype to the mice, such as immune parameters, sex hormones, neuronal activity (and morphology, e.g., neurite outgrowth, spines, etc.), and gene expression (e.g., Rbfox1 from prior studies and novel candidates from C01 and C04).

Beta-hydroxy-butyrate (BHB), a ketone body, is negatively associated with aggressive behavior. BHB is a metabolite and an active signaling substrate involved in epigenetic regulation of e.g., neurotrophic factor genes in the brain. Of the three main ketone bodies, acetone, acetoacetate and BHB, acetone is a very volatile compound, mainly eliminated through respiration, thus can be measured non-invasively in breath. A reduction of acetone in breath has been found to highly correlate with BHB in blood and be associated with symptom severity in schizophrenia (Jiang et al. 2022). Using MR spectroscopy, A08 aims to (1) identify whether acetone and other volatile organic compounds in breath are associated with aggression and acute threat processing in mental disorders and (2) to examine whether these breath markers are associated with direct metabolic brain correlates (like BHB, glutamate) and with the brain-derived neurotrophic factor (BDNF) levels in plasma. In a translational approach, (3) we will test if supplementation of BHB reduces aggressive behavior in mice.

Sex-dependent effects and gene-environment interactions will be investigated by applying escalating aggression paradigms. Specifically, the project will investigate the effects of early life stress on aggression in response to threat and hyperactivity as well as social decision-making in 32 BXD mouse strains, the progenitor strains (C057Bl/6J and DBA/2J), and the F1 BXD cross. The project aims to identify the quantitative trait loci (QTL) and putative candidate genes contained within the QTL and associate them with specific behavioral responses of stressed and unstressed cohorts of mice. The publicly available database GeneNetwork (www.genenetwork.org) will be used to validate the findings which include measurements of mRNA and protein expression, and methylation patterns in mouse brains

Bundle all training and mentoring activities in a research training group (RTG) for the young researchers participating in this collaborative research center.