OSCR

Repeated TLR7 activation induces cell type- and brain region-specific transcriptome changes in male mice.

Overview

Authors: Marion M Friske1,2, Riccardo Barchiesi1,2, Nihal A Salem1,2, Ruth L Allard1,2, Anna C Dobre1,2, Nicholas Rhyan1,2, Wen Chen1,2, R Dayne Mayfield1,2
  1. Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, 2500 Speedway, Austin, TX 78712 USA
  2. Department of Neuroscience, The University of Texas at Austin, 2500 Speedway, Austin, TX 78712 USA
Institutions: The University of Texas at Austin (United States)
Journal: Scientific reports, volume 16, issue 1, article 20115
Dates: received 25 November 2025; accepted 24 April 2026; published online 30 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41598-026-50920-5 · PMID 42062470 · PMCID PMC13324148 · OpenAlex W7159653621
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: genetics / omics (modality), mouse (organism), cellular / molecular (subfield)
Keywords: Molecular biology, Neuroscience
MeSH: Brain*, Membrane Glycoproteins*, Toll-Like Receptor 7*, Transcriptome*, Animals, Astrocytes, Blood-Brain Barrier, Gene Expression Profiling, Imidazoles, Male, Mice, Mice, Inbred C57BL, Neurons, Prefrontal Cortex, Toll-Like Receptor Agonists (* major topic)
Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex
Funding: NIAAA NIH HHS (K99 AA032053); NIH HHS (AA012404, AA020926, K00 AA029955)
Citations: not cited yet (Europe PMC); 86 references in the paper

Abstract

Alcohol consumption triggers neuroinflammation, potentially creating a feed-forward loop that increases drinking. Previous studies have shown that activation of the toll-like receptor 7 (TLR7) leads to escalated drinking. In this study, we aim to identify cell type-specific transcriptomic patterns underlying TLR7-induced neuroinflammation, potentially leading to escalated drinking. Therefore, male C57BL/6J mice were treated with the selective TLR7 agonist R848 every-other day for 20 days in total. After 10 treatment-free days, half of the cohort underwent two bottle-choice drinking; the other half was sacrificed and brains were collected for single-nucleus RNA-Sequencing (snRNA-Seq) in the medial prefrontal cortex (mPFC) and central amygdala (AMG). The AMG showed a greater number of differentially expressed genes (DEGs), primarily in inhibitory and excitatory neurons. Among glial cells, AMG astrocytes exhibited the greatest number of DEGs, which were involved in blood-brain barrier (BBB) regulation (e.g., Cldn5, Mecom, Nrg1), a finding supported by secondary validation using Xenium in situ spatial transcriptomics on AMG-containing sections. BBB-regulatory genes, including those in the Wnt signaling pathway (e.g., Notch3, Top2a, Aldoc), were altered across multiple cell types in both regions. Together with the alterations observed in neurons, these findings suggest that repeated TLR7 activation induces persistent BBB and neuronal dysregulation, potentially leading to TLR7-induced escalated drinking.

Supplementary Information: The online version contains supplementary material available at 10.1038/s41598-026-50920-5.

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

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

Datasets cited

Data availability

Data is uploaded on the Gene Expression Omnibus data repository (accession number: GSE312659 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE312659)) as well as a Shiny App ( [https://wcaar.shinyapps.io/R848/](https:/wcaar.shinyapps.io/R848) ) and will be publicly available the day of publication onwards. Analysis code is available upon reasonable request.

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

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 2 keywords, 15 MeSH terms, 2 funders, 86 references.

Cite

This paper

Friske, M. M., Barchiesi, R., Salem, N. A., Allard, R. L., Dobre, A. C., Rhyan, N., Chen, W., & Mayfield, R. D. (2026). Repeated TLR7 activation induces cell type- and brain region-specific transcriptome changes in male mice. Scientific reports, 16(1), 20115. https://doi.org/10.1038/s41598-026-50920-5

BibTeX

@article{friske2026repeated,
author = {Friske, Marion M and Barchiesi, Riccardo and Salem, Nihal A and Allard, Ruth L and Dobre, Anna C and Rhyan, Nicholas and Chen, Wen and Mayfield, R Dayne},
title = {{Repeated TLR7 activation induces cell type- and brain region-specific transcriptome changes in male mice}},
journal = {Scientific reports},
year = {2026},
month = apr,
volume = {16},
number = {1},
pages = {20115},
publisher = {Nature Publishing Group},
issn = {2045-2322},
doi = {10.1038/s41598-026-50920-5},
url = {https://doi.org/10.1038/s41598-026-50920-5},
pmid = {42062470},
pmcid = {PMC13324148}
}

RIS

TY - JOUR
AU - Friske, Marion M
AU - Barchiesi, Riccardo
AU - Salem, Nihal A
AU - Allard, Ruth L
AU - Dobre, Anna C
AU - Rhyan, Nicholas
AU - Chen, Wen
AU - Mayfield, R Dayne
TI - Repeated TLR7 activation induces cell type- and brain region-specific transcriptome changes in male mice
T2 - Scientific reports
J2 - Sci Rep
PY - 2026
DA - 2026/04/30
VL - 16
IS - 1
SP - 20115
SN - 2045-2322
PB - Nature Publishing Group
DO - 10.1038/s41598-026-50920-5
UR - https://doi.org/10.1038/s41598-026-50920-5
LA - en
ER -

CSL-JSON

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