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Deciphering Motor Dysfunction and Microglial Activation in mThy1-α-Synuclein Mice: A Comprehensive Study of Behavioral, Gene Experssion, and Methylation Changes [RNA-Seq]

GSE275510 Mus musculus (mouse) DNA methylation 20 samples Submitted 2025/03/05 Platform GPL24247
At a glance

DNA methylation · mouse · 20 samples

What it is
DNA methylationChemical marks on DNA that help switch genes on or off.
Organism
Mus musculus (mouse)
Samples
20 samples: 6 × Brain, mThy1-Asyn, 7month, vs 5 × Brain, mThy1-Asyn, 10month, vs 5 × Brain, wildtype, 10month, vs 4 × Brain, wildtype, 7month,Groups 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
Deciphering motor dysfunction and microglial activation in mThy1-α-synuclein mice: a comprehensive study of behavioral, gene expression, and methylation changesFrontiers in molecular neuroscience · 2025
Summary (written by the submitters)
BACKGROUND: Synucleinopathy disorders are characterized by aggregates of α-synuclein (α-syn), which engage microglia to elicit a neuroinflammatory response. However, the influence α-syn has on DNA methylation and gene expression patterns for other genes has not been thoroughly explored. Our objective is to determine gene expression and methylation changes in microglia induced by aggregate α-syn.
Read the full summary ↓
METHODS: Transgenic mThy1-Asyn mice overexpressing human α-syn are a model of synucleinopathy. Microglia from 7 and 10-month-old mice were used to isolate nucleic acids for methylated DNA and RNA-sequencing. α-Syn-induced changes in gene expression and genomic methylation were determined and examined for pathway and functional enrichment. RESULTS: Microglial DNA isolated from our 7-month cohort had 6,712 differentially methylated regions (DMR), while RNA levels demonstrated a change in 1,141 differentially expressed genes (DEGs) between mThy1-Asyn mice and wild-type littermate controls. The 7-month DEGs and DMRs were highly associated with neuroinflammation likely via TLR pathways. We observed 8,531 DMRs and 1,686 DEGs in 10-month mThy1-Asyn mice. These genes were often predicted by Ingenuity Pathway Analysis to demonstrate inhibition of previously activated inflammatory pathways at 7 months. CONCLUSION: We observed significant α-syn-induced methylation and gene expression changes in microglia. Our data suggest that α-syn overexpression initiates microglial activation leading to neuroinflammation and cellular metabolic stresses, which is associated with disease progression.
Published in
Deciphering motor dysfunction and microglial activation in mThy1-α-synuclein mice: a comprehensive study of behavioral, gene expression, and methylation changes
McGregor BA, Raihan MO, Brishti A et al. · Frontiers in molecular neuroscience 2025 · PMID 40018011 · doi:10.3389/fnmol.2025.1544971
This dataset
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.

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 GSE275510_RAW.tar (it can run to tens of gigabytes).

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.

What the files usually look like: Look for beta-value tables or raw IDAT files among the supplementary files.

Also filed as BioProject PRJNA1151598 and SRA study SRP528234. Searching any of these in the dataset finder brings you back here.

Study design
6 × Brain, mThy1-Asyn, 7month, vs 5 × Brain, mThy1-Asyn, 10month, vs 5 × Brain, wildtype, 10month, vs 4 × Brain, wildtype, 7month,

Supports a between-group comparison across 20 samples.

How we read this: 4 replicated groups read from 20 sample titles; they account for 20 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
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