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Single-nucleus RNA Sequencing Reveals GABAergic Vulnerability and Reactive Gliosis Driven by Loss of TDP-43

GSE309401 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2025/10/06 Platform GPL24247
Summary
TDP-43 is an RNA-binding protein important for RNA processing, whose loss-of-function is involved in multiple neurodegenerative disorders, including frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease (AD). We performed single-nucleus RNA-sequencing to study the convergent and divergent molecular signatures of short-term and long-term TDP-43 depletion in the medial prefrontal cortex (mPFC) using Tdp-43F/F mice, compared with that of 5xFAD mice, a well-established AD mouse model with β-amyloid plaque pathology. Our results demonstrated a significant loss of GABAergic neurons in the mPFC after short-term TDP-43 depletion. This was accompanied by a remarkable reactive gliosis in the mPFC. Our results revealed a strong GABAergic and glial involvement during early stages of TDP-43 loss-of-function, suggesting that the GABAergic system is vulnerable to TDP-43 pathology and could be considered a potential target for developing therapeutic strategies and biomarkers for early detection in TDP-43 linked AD-related dementia.
Published in
Single-nucleus RNA sequencing reveals GABAergic vulnerability and reactive gliosis driven by loss of TDP-43
Thapa R, Adhikari N, Gautam S et al. · iScience 2025 · PMID 41210976 · doi:10.1016/j.isci.2025.113745
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Also filed as BioProject PRJNA1335961 and SRA study SRP629445. Searching any of these in the dataset finder brings you back here.

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