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GSE207251

GSE GEO
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Prions induce an early Arc response in the hippocampus of prion-infected mice

Organism: Mus musculus
Platform: GPL21103
Samples: 6
Experiment Types:
Expression profiling by high throughput sequencing
Submitted: Jun 30 2022
Last Updated: May 02 2023
Status: Public on Jan 01 2023
Contact: Christina,,Sigurdson (UC San Diego)

Relations

BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA854376

Summary

Synapse dysfunction and synaptic loss are a central feature of neurodegenerative disorders, including prion disease. The cellular prion protein (PrPC) binds prion, amyloid-β, tau, and α-synuclein oligomers, resulting in the activation of macromolecular complexes and signaling at the post-synapse, yet the initial signaling events are unclear. Here we used a transcriptomic approach focused on the early-stage, prion-infected hippocampus of male wild type mice, and identify immediate early genes, including the synaptic activity response gene, Arc/Arg3.1, as significantly upregulated. In a longitudinal study of the prion-infected hippocampus, Arc/Arg-3.1 protein increased, from early to terminal disease. Notably, metabotropic glutamate receptor levels (mGluR5 dimers) were markedly reduced over time, while phosphorylated AMPA receptors (pGluA1-S845) levels increased. Sporadic Creutzfeldt-Jakob disease (sCJD) post-mortem cortical samples also showed low levels of mGluR5 dimers. Together, these findings suggest that prions trigger a chronic Arc response, an increase in phosphorylated GluA1, and a reduction in mGluR5 receptors beginning in early disease.

Overall Design

RNA-seq for prion (22L strain)- or mock-inoculated C57/BL6J male mice at 63 days post inoculation or 40% in disease progression to terminal disease

Analysis (4 steps)

View Data Processing
Processing steps for GSE207251
  1. Adapters trimmed with cutadapt (v1.4.0)
  2. Reads mapping to repetitive elements (RepBase v18.04) with STAR were removed
  3. Remaining reads were mapped to mouse genome mm9 with STAR (v2.4.0i)
  4. FeatureCounts was used to assign reads to genes (v1.5.0)

Supplementary Files (2)

GSE207251_deseq2_results.csv.gz Download
GSE207251_tpm_filtered.csv.gz Download
GEO Samples (6)

Dataset Citations (1)

Prions induce an early Arc response and a subsequent reduction in mGluR5 in the hippocampus.
PMID 35905927 · 2022 · Neurobiology of disease
Daniel Ojeda-Juárez, Jessica A Lawrence, Katrin Soldau, Donald P Pizzo, Emily Wheeler, Patricia Aguilar-Calvo, Helen Khuu, Joy Chen, Adela Malik, Gail Funk, Percival Nam, Henry Sanchez, Michael D Geschwind, Chengbiao Wu, Gene W Yeo, Xu Chen, Gentry N Patrick, Christina J Sigurdson

SRA Experiments (6) and Runs (6)

Total: 11103 MB
SRX15950427 SRP384336 RNA-Seq PAIRED
GSM6283031: Prion1; Mus musculus; ssRNA-seq
Sample: SRS13637086
BioProject: PRJNA854376
BioSample: SAMN29438819
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Mus musculus
Sample attributes
source_name: Hippocampus
tissue: Hippocampus
strain: C57BL/6
Sex: male
genotype: Wild type
treatment: prion (22L stain) intracraneal inoculation
Original files (1)
Hippocampus
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR19907652 25997031 5251400262 1641.89 2712_1_S25_L003_R1_001.fastq.gz, 2712_1_S25_L003_R2_001.fastq.gz, SRR… SRA
SRX15950428 SRP384336 RNA-Seq PAIRED
GSM6283032: Prion2; Mus musculus; ssRNA-seq
Sample: SRS13637087
BioProject: PRJNA854376
BioSample: SAMN29438818
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Mus musculus
Sample attributes
source_name: Hippocampus
tissue: Hippocampus
strain: C57BL/6
Sex: male
genotype: Wild type
treatment: prion (22L stain) intracraneal inoculation
Original files (1)
Hippocampus
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR19907651 36115239 7295278278 2293.4 2712_2_S26_L003_R1_001.fastq.gz, 2712_2_S26_L003_R2_001.fastq.gz, SRR… SRA
SRX15950429 SRP384336 RNA-Seq PAIRED
GSM6283033: Prion3; Mus musculus; ssRNA-seq
Sample: SRS13637088
BioProject: PRJNA854376
BioSample: SAMN29438817
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Mus musculus
Sample attributes
source_name: Hippocampus
tissue: Hippocampus
strain: C57BL/6
Sex: male
genotype: Wild type
treatment: prion (22L stain) intracraneal inoculation
Original files (1)
Hippocampus
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR19907650 26366642 5326061684 1675.98 2712_3_S27_L003_R1_001.fastq.gz, 2712_3_S27_L003_R2_001.fastq.gz, SRR… SRA
SRX15950430 SRP384336 RNA-Seq PAIRED
GSM6283034: Mock2; Mus musculus; ssRNA-seq
Sample: SRS13637089
BioProject: PRJNA854376
BioSample: SAMN29438816
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Mus musculus
Sample attributes
source_name: Hippocampus
tissue: Hippocampus
strain: C57BL/6
Sex: male
genotype: Wild type
treatment: mock intracraneal inoculation
Original files (1)
Hippocampus
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR19907649 31646862 6392666124 2004.73 2713_2_S28_L003_R1_001.fastq.gz, 2713_2_S28_L003_R2_001.fastq.gz, SRR… SRA
SRX15950431 SRP384336 RNA-Seq PAIRED
GSM6283035: Mock3; Mus musculus; ssRNA-seq
Sample: SRS13637090
BioProject: PRJNA854376
BioSample: SAMN29438815
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Mus musculus
Sample attributes
source_name: Hippocampus
tissue: Hippocampus
strain: C57BL/6
Sex: male
genotype: Wild type
treatment: mock intracraneal inoculation
Original files (1)
Hippocampus
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR19907648 30107994 6081814788 1924.22 2713_3_S29_L003_R1_001.fastq.gz, 2713_3_S29_L003_R2_001.fastq.gz, SRR… SRA
SRX15950432 SRP384336 RNA-Seq PAIRED
GSM6283036: Mock4; Mus musculus; ssRNA-seq
Sample: SRS13637091
BioProject: PRJNA854376
BioSample: SAMN29438814
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Mus musculus
Sample attributes
source_name: Hippocampus
tissue: Hippocampus
strain: C57BL/6
Sex: male
genotype: Wild type
treatment: mock intracraneal inoculation
Original files (1)
Hippocampus
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR19907647 24602138 4969631876 1562.6 2713_4_S30_L003_R1_001.fastq.gz, 2713_4_S30_L003_R2_001.fastq.gz, SRR… SRA

Linked Publications (2)

Data Files (6)

Accession File Name Stored Type Output Type Mapping Assembly Size Download
2712_1_S25_L003_R1_001.fastq.gz RNA-Seq 1.6 GB link
2712_2_S26_L003_R1_001.fastq.gz RNA-Seq 2.2 GB link
2712_3_S27_L003_R1_001.fastq.gz RNA-Seq 1.6 GB link
2713_2_S28_L003_R1_001.fastq.gz RNA-Seq 2.0 GB link
2713_3_S29_L003_R1_001.fastq.gz RNA-Seq 1.9 GB link
2713_4_S30_L003_R1_001.fastq.gz RNA-Seq 1.5 GB link