Impaired mitochondrial complex I function as a candidate driver in the biological stress response and a concomitant stress-induced brain metabolic reprogramming in male mice.

Mitochondria play a critical role in bioenergetics, enabling stress adaptation, and therefore, are central in biological stress responses and stress-related complex psychopathologies. To investigate the effect of mitochondrial dysfunction on the stress response and the impact on various biological domains linked to the pathobiology of depression, a novel mouse model was created. These mice harbor a gene trap in the first intron of the Ndufs4 gene (Ndufs4GT/GT mice), encoding the NDUFS4 protein, a structural component of complex I (CI), the first enzyme of the mitochondrial electron transport chain. We performed a comprehensive behavioral screening with a broad range of behavioral, physiological, and endocrine markers, high-resolution ex vivo brain imaging, brain immunohistochemistry, and multi-platform targeted mass spectrometry-based metabolomics. Ndufs4GT/GT mice presented with a 25% reduction of CI activity in the hippocampus, resulting in a relatively mild phenotype of reduced body weight, increased physical activity, decreased neurogenesis and neuroinflammation compared to WT littermates. Brain metabolite profiling revealed characteristic biosignatures discriminating Ndufs4GT/GT from WT mice. Specifically, we observed a reversed TCA cycle flux and rewiring of amino acid metabolism in the prefrontal cortex. Next, exposing mice to chronic variable stress (a model for depression-like behavior), we found that Ndufs4GT/GT mice showed altered stress response and coping strategies with a robust stress-associated reprogramming of amino acid metabolism. Our data suggest that impaired mitochondrial CI function is a candidate driver for altered stress reactivity and stress-induced brain metabolic reprogramming. These changes result in unique phenomic and metabolomic signatures distinguishing groups based on their mitochondrial genotype.

Modelling potential landscape sediment delivery due to projected soybean expansion: a scenario study of the Balsas sub-basin, Cerrado, Maranhão state, Brazil.

In Brazil, agriculture expansion is taking place primarily in the Cerrado ecosystems. With the aim of supporting policy development and protecting the natural environment at relevant hotspots, a scenario study was conducted that concerned not only land-use change, but also the resulting effects on erosion and deposition. This coupled approach helped to evaluate potential landscape impacts of the land-use scenarios. In the study area, the Balsas sub-basin in Maranhão State, a model chain was used to model plausible future soybean expansion locations (CLUE-S model) and resulting sediment mobilization patterns (LAPSUS model) for a business-as-usual scenario. In the scenario, more erosion occurred in areas where the conversion of natural vegetation into soybean cultivation is likely to take place, but the generated sediments tended to accumulate mainly within the conversion areas, thus limiting the offsite effects of the increased erosion. These results indicated that when agricultural expansion is kept away from rivers, Cerrado conversion will have only a limited impact on the sediment loads of local rivers. Where land-use changes are most concentrated are coincident with areas where more new sediments are generated (higher erosion) and where more sediments are re-deposited.