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Impairment of hippocampal gamma oscillations, mitochondria and neurovascular function in CADASIL

GSE300114 Mus musculus (mouse) Single-cell RNA-seq 11 samples Submitted 2026/02/06 Platform GPL30172
At a glance

Single-cell RNA-seq · mouse · 11 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Mus musculus (mouse)
Samples
11 samples: 3 × brain vasc_Tg350_9 months, vs 3 × brain vasc_Tg350_6 months, vs 3 × brain vasc_Tg100_6 months, vs 2 × brain vasc_Tg100_9 months,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
Impairment of hippocampal gamma oscillations, mitochondria and neurovascular function in CADASILBrain : a journal of neurology · 2026
Summary (written by the submitters)
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a small vessel disease caused by NOTCH3 gene mutations, leading to vascular smooth muscle cell degeneration, arteriopathy, and subcortical ischemic infarcts. Many CADASIL patients, however, also develop cognitive impairment, indicating that neuronal functions are disturbed, but less is known about the cellular and molecular basis of these aspects in CADASIL.
Read the full summary ↓
In this study, we used a humanized CADASIL mouse model harbouring the R182C mutation (R182C-TgN3), post-mortem human CADASIL brain sections with three different NOTCH3 gene mutations and primary human vascular smooth muscle cells harbouring the R133C NOTCH3 mutation as primary cellular models to characterise the neurovascular contribution to cognitive impairment. To specifically evaluate neuronal, mitochondrial and neurovascular function, we performed ex vivo electrophysiology, immunohistochemistry (confocal and iDISCO+ methods), western blotting, Seahorse assay, quantitative polymerase chain reaction (qPCR), and single-cell RNA sequencing. In CADASIL mice, hippocampal gamma oscillation patterns were impaired along with significant decreases in neuronal fiber length and aberrant neuronal morphology. The latter two phenotypes were also observed in post-mortem human brain tissue from CADASIL patients. Consistent with these findings, we noted significantly lower levels of mitochondrial respiratory complexes in the CADASIL mouse hippocampus, isolated mouse brain vessels and primary human vascular smooth muscle cells. Human vascular smooth muscle cells exhibited reduced oxygen consumption rates leading to reduced ATP production as well as decreased glycolytic capacity in conjunction with increased pro-inflammatory gene expression, suggesting a broader impact on cellular energy metabolism and a neuroinflammatory process. In the CADASIL mice, we also observed extensive accumulation of the NOTCH3 extracellular domain on hippocampal vessels. Light sheet imaging with iDISCO+ clearing demonstrated substantial vascular smooth muscle cell loss and reduced vessel density in the hippocampus at 9 months of age. Additionally, 3D imaging showed increased microglial attachment to vessels and enlargement of the size of the vessel-associated microglia in CADASIL mice. Single-cell RNA sequencing revealed a microglial subcluster expressing genes involved in mitochondria respiration and inflammation. Collectively, our results reveal that exacerbated vascular network damage may mediate cognitive decline observed in the later stages of CADASIL and highlight the critical role of the neurovascular unit. Our findings provide valuable insights into the underlying mechanisms of neuronal dysfunction and pave the way for future research and potential therapeutic strategies.
Published in
Impairment of hippocampal gamma oscillations, mitochondria and neurovascular function in CADASIL
Shao W, Oliveira DV, Naia L et al. · Brain : a journal of neurology 2026 · PMID 41622715 · doi:10.1093/brain/awag033
This dataset
Open GSE300114 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 GSE300114_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1279044 and SRA study SRP592854. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41622715) ↗
Study design
3 × brain vasc_Tg350_9 months, vs 3 × brain vasc_Tg350_6 months, vs 3 × brain vasc_Tg100_6 months, vs 2 × brain vasc_Tg100_9 months,

Supports a between-group comparison across 11 samples.

How we read this: 4 replicated groups read from 11 sample titles; they account for 11 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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