Translation: The University of Toledo Journal of Medical Sciences

The effects of the ketone body ?-hydroxybutyrate on the neuronal transcriptome

Zayn Cheema — 2025-02-05

The ketogenic diet is emerging as an effective therapeutic option for patients with neurological disorders. The diet results in metabolism of fatty acids to ketone bodies like ?-hydroxybutyrates (BHBs), which serve as an alternative fuel source for brain cells. However, the molecular effect of BHB on neurons is not well understood. We hypothesized that BHB administration will induce upregulation of energy metabolism-related processes in neurons. To assess the effect of BHB administration on the neuronal transcriptome, we reanalyzed a publicly available RNAseq dataset (GSE252513) using a bioinformatic “3-pod” approach. We conducted pathway analysis and identified leading edge genes using Gene Set Enrichment Analysis (GSEA) and conducted chemical perturbagen analysis using the iLINCS repository to identify drugs that are concordant and discordant with BHB administration. We identified significantly altered (p<0.05) pathways associated with inflammation and immunity such as “regulation of proinflammatory cytokine production” and “modulation of inflammatory responses.” We did not identify significant modulation of energy metabolism-related pathways in response to BHB administration. Our results suggest that under normal conditions, BHBs primary actions include modulation of cellular neuronal immune responses.

Low dose deltamethrin exposure affects gene expression in rat frontal cortex

Junze Wu — 2025-02-05

Pyrethroids are a class of commonly used synthetic insecticides, widely used in agricultural and residential settings due to their efficacy and relatively low environmental impact. Nonetheless, epidemiological studies have found that exposure to pyrethroids during developmental stages is linked to risk for neurodevelopmental disorders. However, the molecular mechanisms behind these neurotoxic effects remain unclear. Our study investigates the impact of oral exposure to deltamethrin, a widely used Type II pyrethroid pesticide, on gene expression in the frontal cortex of rats. We used differential gene expression data from frontal cortex dissections from male Long-Evans rats exposed to a 3 mg/kg oral dose of deltamethrin (or vehicle) to perform a 3Pod analysis in R Studio, which included GSEA, Enrichr, and iLINCS analyses. We found that rats who were exposed to deltamethrin had significant changes in gene expression in cortex in pathways related to inflammation, apoptosis, cellular energy metabolism, and synapses. Our study provides important insight on the effects of pesticide exposure on the brain and possible treatments and preventions. This study also emphasizes the need for further research on pyrethroid pesticides and their relationship to neurodevelopmental disorders.

Borrelia burgdorferi Tolerance-Associated Changes in Gene Expression of Murine Macrophages

Sophia Chen — 2025-02-05

Lyme disease, caused by the spirochete Borrelia burgdorferi (Bb), is the most prevalent vector-borne disease in the United States. Macrophages, key cellular players in the innate immune response, exhibit diminished functionality over time during Bb infection, potentially leading to chronic infection. This study explores the transcriptional changes associated with macrophages that develop tolerance to Bb. Using RNA sequencing of murine bone marrow-derived macrophages exposed to Bb, we identified differentially expressed genes and dysregulated pathways between productively stimulated and tolerized macrophages. Key findings revealed significant downregulation of type-I interferon signaling and associated immune responses, suggesting mechanisms of immune tolerance. Additionally, connectivity analysis identified potential drug candidates for repurposing to enhance macrophage activity. Our results underscore the complexity of macrophage responses to Bb and provide a foundation for future research to develop targeted therapies aimed at modulating immune responses and improving treatment outcomes for Lyme disease patients. Ultimately, these findings offer new insights into the pathogenesis and potential treatment strategies for Lyme disease.