Epigenetic changes associated with the progression of prion disease in Syrian hamsters (<i>Mesocricetus auratus</i>).

Overview

1. Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN, USA
2. Minnesota Center for Prion Research and Outreach, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA
3. Department of Animal Science, University of Minnesota, St. Paul, MN, USA
4. Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, NE, USA

Abstract

Prion diseases are fatal neurodegenerative disorders characterized by abnormally folded prion proteins inducing misfolding of normal prion proteins, leading to neurotoxic fibrils and plaques. Epigenetic mechanisms, particularly DNA methylation, are increasingly implicated in prion-like diseases (e.g. Alzheimer’s disease), but their role in prion pathogenesis remains unclear. To investigate, we used nanopore sequencing and RNAseq to measure genome-wide methylation and gene expression in the brains of Syrian hamsters (Mesocricetus auratus) experimentally infected with a hamster-adapted murine synthetic prion strain (n = 9) and age-matched mock-infected controls (n = 9) at 80, 120, and 160 days post-infection (dpi). We identified 1,586, 1,692, and 2,429 differentially methylated regions (DMRs) at 80, 120, and 160 dpi, respectively. Early- and mid-stage prion disease (80 and 120 dpi) skewed towards hypermethylation, whereas late-stage prion disease (160 dpi) skewed towards hypomethylation. Gene ontology (GO) of DMR-associated genes at 160 dpi included neuron regulation and signalling, neurodevelopment, and cellular stress pathways. We identified 178 differentially expressed genes (DEGs) at 80 dpi, 90 at 120 dpi, and 616 at 160 dpi. The majority of DEGs were downregulated at 80 dpi, and at 120 and 160 dpi, most were upregulated. Overlap in DEGs across timepoints was limited, and GO terms were related to upregulation of disease/injury response and cell death pathways in later timepoints. Overall, we found a stage-specific transcriptional shift from immune suppression to widespread immune and inflammation activation. These findings provide time-resolved data on methylation and transcriptional changes associated with impaired neuronal structure, function, and communication during disease.

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Data

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• figshare:33201798, at figshare; found in DataCite

Data availability statement

The datasets generated and analysed during the current study are available in the NCBI’s Sequence Read Archive (SRA) under BioProject number PRJNA1482062. Detailed computational methods used in this workflow are included in the supplementary data (Supplemental Data 1). Additional data is provided within the supplementary information files.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 4 keywords, 8 MeSH terms, 2 funders, 85 references.

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This paper

Frank, L. E., Flack, N., Faulk, C., Block, A. J., Bartz, J. C., & Larsen, P. A. (2026). Epigenetic changes associated with the progression of prion disease in Syrian hamsters (<i>Mesocricetus auratus</i>). Prion, 20(1), 52-65. https://doi.org/10.1080/19336896.2026.2710965

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