GEO series

Intranasal delivery of SARS-CoV-2 triggers cellular and molecular alterations in the mouse trigeminal ganglion and brainstem: focus on the nociceptive pathways related to migraine

GSE308948 Mus musculus (mouse) RNA-seq (gene expression) 18 samples Submitted 2026/04/01 Platform GPL34328

At a glance

RNA-seq (gene expression) · mouse · 18 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 18 samples: 7 × Brainstem_infected vs 5 × trigeminal_ganglion_infected vs 3 × trigeminal_ganglion_mock vs 3 × Brainstem_mockGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Intranasal SARS-CoV-2 infection changes the transcriptome of the mouse trigeminal ganglion and brainstem: potential mechanisms underlying headache and trigeminal pain presentation in COVID-19Journal of neuroinflammation · 2026

Summary (written by the submitters)

Headache disorders, including migraine, are common symptoms of COVID-19, which may result from the sensitization of the trigeminal ganglion (TG) and brainstem relay structures. Recent studies suggest that SARS-CoV-2 may invade trigeminal nerve endings in the nasal cavity. However, despite these insights, the precise underlying mechanisms remain poorly understood.

Read the full summary ↓

Here, we investigated the cellular and molecular changes in the TG and brainstem with a special attention for the spinal trigeminal nucleus in K18-hACE2 mouse model infected with SARS-CoV-2. We first confirmed the expression of the cellular proteins playing a role in SARS-CoV-2 cell entry (ACE2, TMPRSS2 and NRP1) in both structures. In addition, we reported the expression of the viral nucleocapsid (N) and spike (S) proteins in TG and brainstem at 6 days post infection by multimodal approaches (RNA sequencing, RNAscope, and immunohistofluorescence). In the TG, SARS-CoV-2 proteins S and N were detected in nerve fibers as well as in transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) nociceptive neurons. Transcriptomics analysis of the TG from infected K18-hACE2 have revealed significant changes in gene expression, including Ccl2, Atf3, Cxcl10, Saa3, Plin4 genes. Additionally, increased immunoreactivity for ATF3 and Iba1 has been detected in the TG of these mice post-infection. In the brainstem, SARS-CoV-2 protein was exclusively found in neurons, with no detection in astrocytes or microglial cells, the latter exhibiting an activated form in K18-hACE2 infected mice. Bulk RNA-Seq analysis clearly confirmed a cytokine and chemokine storms, inflammasome activation (Gsdmd, Casp4/1, Nlrp3), molecular markers of neuronal activation (Jun, Fos, Fosb), neuronal injury (Atf3) and pain markers (Gfra1, Ntrk1, Ptgs2). We also shown that a significant number of infected neurons were found within, or in close contact to a dense network of CGRP-positive nociceptive nerve fibers in the trigeminal brainstem. Finally, we provided gene interaction networks and identified specific SARS-CoV-2 biomarkers Saa3, Cxcl10, Ccl2, Atf3 and Plin4 in TG and brainstem which could serve as potential indicators of disease severity. In conclusion, this study reports a robust set of transcriptomic and cellular changes triggered by SARS-CoV-2 in the TG and brainstem, offering a potential mechanistic explanation for sensory abnormalities, such as migraine, observed in COVID-19 patients.

Published in

Intranasal SARS-CoV-2 infection changes the transcriptome of the mouse trigeminal ganglion and brainstem: potential mechanisms underlying headache and trigeminal pain presentation in COVID-19

Huang J, Reboussin E, Bianchi L et al. · Journal of neuroinflammation 2026 · PMID 41692789 · doi:10.1186/s12974-026-03722-5

This dataset

Open GSE308948 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE308948_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1333474 and SRA study SRP625658. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41692789) ↗

Study design

7 × Brainstem_infected vs 5 × trigeminal_ganglion_infected vs 3 × trigeminal_ganglion_mock vs 3 × Brainstem_mock

Supports a case/control comparison: 12 samples read as cases, 6 as controls.

How we read this: 4 replicated groups read from 18 sample titles; they account for 18 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM9256629 trigeminal_ganglion_mock_rep1 trigeminal_ganglion_mock
GSM9256630 trigeminal_ganglion_mock_rep2 trigeminal_ganglion_mock
GSM9256631 trigeminal_ganglion_mock_rep3 trigeminal_ganglion_mock
GSM9256632 trigeminal_ganglion_infected_rep1 trigeminal_ganglion_inf…
GSM9256633 trigeminal_ganglion_infected_rep2 trigeminal_ganglion_inf…
GSM9256634 trigeminal_ganglion_infected_rep3 trigeminal_ganglion_inf…
GSM9256635 trigeminal_ganglion_infected_rep4 trigeminal_ganglion_inf…
GSM9256636 trigeminal_ganglion_infected_rep5 trigeminal_ganglion_inf…
GSM9256637 Brainstem_mock_rep1 Brainstem_mock
GSM9256638 Brainstem_mock_rep2 Brainstem_mock
GSM9256639 Brainstem_mock_rep3 Brainstem_mock
GSM9256640 Brainstem_infected_rep1 Brainstem_infected
GSM9256641 Brainstem_infected_rep2 Brainstem_infected
GSM9256642 Brainstem_infected_rep3 Brainstem_infected
GSM9256643 Brainstem_infected_rep4 Brainstem_infected
GSM9256644 Brainstem_infected_rep5 Brainstem_infected
GSM9256645 Brainstem_infected_rep6 Brainstem_infected
GSM9256646 Brainstem_infected_rep7 Brainstem_infected

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