Biology subjects

Wichern, F.

Publications and source records attributed to Wichern, F..

4 recordsLinked to original sources

bioRxiv2026

Semaglutide Attenuates Neuroinflammation in Mice

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown promise in preclinical models of neurodegeneration, with emerging evidence suggesting these effects may be driven by modulation of neuroinflammation. However, the cellular mechanisms underlying GLP-1 RA effects on neuroinflammation remain poorly understood. Here, using a mouse model of lipopolysaccharide-induced neuroinflammation, we investigated how semaglutide coordinates cellular responses to resolve neuroinflammation. We find that semaglutide prevents brain infiltration of neutrophils, excessive cytokine release, and suppresses neuroinflammation-associated transcriptional signatures specifically in microglia, endothelial cells, and a subset of pericytes. Mechanistically, we identify a subset of Glp1r-expressing neurons in the dorsal vagal complex that, upon semaglutide treatment, regulate genes involved in anti-inflammatory signaling. Semaglutide-modulated pathways overlap with inflammatory signatures found in human neurodegenerative diseases, including Alzheimers disease, suggesting broad relevance for conditions involving neuroinflammation. Together, these findings reveal how GLP-1R signaling orchestrates resolution of neuroinflammation through coordinated multi-cellular programs.

neuroscience↗

bioRxiv2025

Soil microbiome predator diversity outperforms nitrogen addition in boosting plant biomass via bacterial community shifts

Nitrogen (N) is crucial for plant growth, but its overuse harms biodiversity. Increasing soil biodiversity might provide the means to reduce N inputs, but experimental evidence for this paradigm-shift is limited. Using microbiome predators (protists and nematodes) that shape microbiome composition and release N, we examined how interactions between their diversity and N addition affect Cannabis sativa growth. Microbiome predator addition overall boosted plant biomass by up to 53%, particularly under low N conditions, primarily by altering bacterial community composition and enriching functions related to carbon and N cycling. In turn, microbiome predator diversity had the strongest effect on biomass production, while N levels played a greater role in determining plant nutrient content. These findings suggest that increased microbiome predator diversity can reduce the plants dependency on added N, showing the pivotal role of soil biodiversity in enhancing plant performance and serving as tools to mitigate N inputs.

ecology↗

bioRxiv2025

Transferrin receptor-binding blood-brain barrier shuttle enhances brain delivery and efficacy of a therapeutic anti-Abeta antibody

Transferrin receptor-1 (TfR1) transcytosis-mediated delivery of therapeutic monoclonal antibodies across the blood-brain barrier (BBB) is a promising concept in drug development for CNS disorders. We sought to investigate brain delivery and efficacy of Aducanumab (Adu), an anti-A{beta} antibody, when fused to a mouse TfR1-binding Fab fragment as BBB shuttle (TfR1-Adu). Automated 3D light sheet fluorescence imaging coupled with computational analysis was applied to evaluate drug IgG distribution and plaque counts throughout the intact brain of transgenic APP/PS1 mice. TfR1-Adu demonstrated enhanced brain delivery and more homogeneous distribution after both acute and chronic dosing in transgenic APP/PS1 mice compared with unmodified Adu. Also, importantly, only unmodified Adu showed perivascular labelling. While high-dose Adu promoted A{beta} plaque depletion in multiple brain regions, similar plaque-clearing efficacy was achieved with a five-fold lower dose of TfR1-Adu. Furthermore, low-dose TfR1-Adu demonstrated greater capacity to reduce congophilic plaque burden. Collectively, these observations strongly support the applicability of TfR1-enabled BBB shuttle strategies to improve brain delivery and plaque-clearing efficacy while mitigating the risk of vascular-associated amyloid-related imaging abnormalities (ARIA) adverse effects associated with current A{beta} immunotherapeutics.

neuroscience↗

bioRxiv2020

The household resistome - frequency of beta-lactamases, class 1 integron and antibiotic resistant bacteria in the domestic environment

The widespread of antibiotic resistance (ABR) among bacteria has become a global health concern for humans, animals and the environment. In this respect, beta-lactams and colistin are of particular interest due to the emergence of multidrug-resistant gram-negative bacteria. Households provide a habitat for bacteria originating from humans, animals, foods, contaminated clothes or other sources in which detergents and biocides are frequently used. Thus, bacteria carrying antibiotic resistance genes (ARGs) might be introduced into private households and may consequently be also released from households to the environment via domestic wastewater. Since data on ABR in the domestic environment is limited, this study aimed to determine the abundance and correlation of beta-lactamase, mobile colistin resistance and class 1 integron genes and to characterize phenotypic resistant strains in private households in Germany. Additionally, the persistence of ABR bacteria to laundering and automated dishwashing was assessed. Shower drains, washing machines and dishwashers were sampled and analyzed using quantitative real-time PCR. Resistant strains were isolated, followed by identification and antibiotic susceptibility testing using VITEK 2. The results show a significantly higher occurrence of ARGs in shower drains compared to washing machines and dishwashers. Several beta-lactamase genes co-occurred and resistance of bacterial isolates correlated positively with genotypic resistance. Laundering and automated dishwashing reduced ABR bacteria significantly and the efficacy increased with increasing duration and temperature. Overall, the domestic environment seems to represent a potential reservoir of beta-lactamase genes and beta-lactam resistant bacteria with shower drains as the dominant source of ABR. ImportanceThe abundance of ABR bacteria and ARGs is steadily increasing and has been comprehensively analyzed in natural environments, animals, foods or wastewater treatment plants. Despite of their connection to these environments, private households seem to be neglected. Therefore, the present study investigated shower drains, washing machines and dishwashers as possible sites of ARGs and ABR bacteria. The analysis of the domestic environment as a potential reservoir of resistant bacteria is crucial to determine whether households contribute to the spread of ABR or are a habitat where resistant bacteria from the environment, humans, food or water accumulate.

microbiology↗