Biology subjects

Engmann, O.

Publications and source records attributed to Engmann, O..

3 recordsLinked to original sources

bioRxiv2026

Aging reprograms the response to chronic stress

Chronic stress is thought to accelerate brain aging. We find this to be true in the brains of young mice, but reversed in the old. Using chronic variable stress in young (2-month) and aged (24-month) mice, we show that aged animals perceive stress physiologically but exhibit stress-responses that differ from those of young mice on behavioral, synaptic, and molecular levels. Multi-Omics profiling of prefrontal cortex and nucleus accumbens and 3D vasculature measurements reveals that stress in aged mice activates angiogenic programs that oppose aging-related patterns. Our results demonstrate that stress cannot be universally conceptualized as an aging accelerator, but instead engages age-specific programs with opposite directionality in young and old animals.

neuroscience↗

bioRxiv2024

Transthyretin orchestrates vitamin B12-induced stress resilience

Chronic stress significantly contributes to mood- and anxiety disorders. Previous and current data suggest a correlative connection between vitamin B12 supplementation, depression, and stress resilience. However, the underlying mechanisms are still poorly understood. This study reveals a molecular pathway that functionally connects vitamin B12, DNA methylation (DNAme), and stress resilience. We identified Transthyretin (Ttr) as a sex-specific key target of vitamin B12 action in chronic stress. Accordingly, TTR expression was increased postmortem in the prefrontal cortex of male, but not female, depressed patients. Virally altered Ttr in the prefrontal cortex functionally contributed to stress- and depression-related behaviors, changes in dendritic spine morphology and gene expression. In stressed mice, vitamin B12 reduced DNAme in the Ttr promoter region. Importantly, using in vivo epigenome editing to alter DNAme in the brains of living mice for the first time, we establish a direct causal link between DNAme on Ttr and stress-associated behaviors. In summary, using state-of-the-art techniques, this study uncovers a mechanistic link between cobalamin supplementation and markers of chronic stress and depression, encouraging further studies into environmental interventions for mood disorders.

neuroscience↗

bioRxiv2024

Npbwr1 signaling mediates fast antidepressant action

Chronic stress is a major risk factor for depression, a leading cause of disability and suicide. Because current antidepressants work slowly, have common side effects, and are only effective in a minority of patients, there is an unmet need to identify the underlying molecular mechanisms. Here, we reveal the receptor for neuropeptides B and W, Npbwr1, as a key regulator of depressive-like symptoms. Npbwr1 is increased in the nucleus accumbens of chronically stressed mice and postmortem in patients diagnosed with depression. Using viral-mediated gene transfer, we demonstrate a causal link between Npbwr1, dendritic spine morphology, the biomarker Bdnf, and depressive-like behaviors. Importantly, microinjection of the synthetic antagonist of Npbwr1, CYM50769, rapidly ameliorates depressive-like behavioral symptoms and alters Bdnf levels. CYM50769 is selective, well tolerated, and shows effects up to 7 days after administration of a single dose. In summary, these findings drastically advance our understanding of mood and chronic stress and warrant further investigation of CYM50769 as a potential fast-acting antidepressant.

neuroscience↗