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Single-nucleus RNA sequencing reveals GABAergic vulnerability and reactive gliosis driven by loss of TDP-43
Rashmi Thapa, Navin Adhikari, Sishir Gautam, Mingming Sun, Sierra McOmie, Viyaleta Davydzenka, Derek Richard SMITH, Jack Syring et al.. iScience, 2025-10-17
Topic: Brain proteins, microglia and lab models
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.
Key findings
- 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.
- 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.
Why it matters
In mice, short-term loss of the TDP-43 protein caused loss of GABAergic neurons and reactive gliosis in a brain region called the medial prefrontal cortex. This is early animal work, and the authors suggest the GABAergic system could be a target for future treatments and biomarkers, but no treatment is available from this yet.
Study details
- Evidence strengthLow
How this study scored 34/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (iScience) |
| Journal's citation record | 1 / 4 | IScience: journal h-index 142 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 1 / 6 | Cited 0.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Yun Li: h-index 18 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41210976) |
| Free to read | 2 / 2 | Free to read |
| Total | 34 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Thapa, R., Adhikari, N., Gautam, S., Sun, M., McOmie, S., Davydzenka, V., et al. (2025). Single-nucleus RNA sequencing reveals GABAergic vulnerability and reactive gliosis driven by loss of TDP-43. iScience. https://doi.org/10.1016/j.isci.2025.113745
Vancouver
Thapa R, Adhikari N, Gautam S, Sun M, McOmie S, Davydzenka V, et al. Single-nucleus RNA sequencing reveals GABAergic vulnerability and reactive gliosis driven by loss of TDP-43. iScience. 2025. doi:10.1016/j.isci.2025.113745. PMID: 41210976.
BibTeX
@article{thapa2025-41210976,
author = {Thapa, Rashmi and Adhikari, Navin and Gautam, Sishir and Sun, Mingming and McOmie, Sierra and Davydzenka, Viyaleta and SMITH, Derek Richard and Syring, Jack and others},
title = {{Single-nucleus RNA sequencing reveals GABAergic vulnerability and reactive gliosis driven by loss of TDP-43}},
journal = {iScience},
year = {2025},
doi = {10.1016/j.isci.2025.113745},
pmid = {41210976},
url = {https://doi.org/10.1016/j.isci.2025.113745}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 18.