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Abnormal behaviors and glial responses in an animal model of tau pathology
Yue Liu, Akira Sobue, Naruhiko Sahara, Madoka Isobe, Rinako Tanaka, Youyun Zhu, Wenjun Zhu, Tetsuo Matsuzaki et al.. Molecular Brain, 2025-11-06
Topic: Brain proteins, microglia and lab models
Tau hyperphosphorylation has been considered a major contributor to neurodegeneration in Alzheimer's disease (AD) and frontotemporal dementia, and related tauopathies have gained prominence in the development of therapies for these conditions. Glial responses are key features of AD and frontotemporal dementia, and are associated with neuroinflammation. Numerous transgenic mouse models that recapitulate critical AD-like pathology and cognitive impairment have been developed to examine pathogenic mechanisms and evaluate therapeutic approaches targeting tau and glial reactivity. Glial reactivity and neuroinflammation coincide with tau hyperphosphorylation, which induces behavioral impairment; however, the specific correlation between glial cell activation and abnormal behavior remains unknown. In this study, we investigated changes in glial cell gene expressions related to abnormal behaviors in rTg4510 mice, which phenocopy the tau pathology, neuroinflammation, and neurodegeneration observed in human tauopathies. Both 4- and 6-month-old rTg4510 mice displayed significantly impaired nest-building behavior compared with control mice. Paired association learning was also impaired in 4-month-old rTg4510 mice. Moreover, rTg4510 mice of both age groups exhibited abnormal exploratory behavior, and these mice spent a longer time in the open arms of the plus-maze test than control mice. Using a magnetic-activated cell-sorting technique, we analyzed glial cell gene expressions related to neuroinflammation, phagocytosis, and amyloid synthesis in the prefrontal cortex of rTg4510 mice. Regression analysis of glial gene expressions and behavioral tests revealed that various glial reactivities were associated with behavioral abnormalities. Our findings suggest specific genetic characteristics of glial cells that may lead to abnormal behavior in rTg4510 mice.
Key findings
- Glial responses are key features of AD and frontotemporal dementia, and are associated with neuroinflammation.
- Both 4- and 6-month-old rTg4510 mice displayed significantly impaired nest-building behavior compared with control mice.
- Regression analysis of glial gene expressions and behavioral tests revealed that various glial reactivities were associated with behavioral abnormalities.
- Our findings suggest specific genetic characteristics of glial cells that may lead to abnormal behavior in rTg4510 mice.
Why it matters
In rTg4510 tau mice, impaired nest-building, learning and exploratory behavior were associated with specific glial gene expression changes. This is animal research that examines links between glial reactivity and behavior and does not test a treatment for people.
Study details
- Evidence strengthLow
How this study scored 38/100
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 (Molecular Brain) |
| Journal's citation record | 1 / 4 | Molecular Brain: journal h-index 99 (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 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.6× 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 | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Hiroyuki Mizoguchi: h-index 50 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Nagoya University: institution h-index 758 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41199342) |
| Free to read | 2 / 2 | Free to read |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13041-025-01252-4
- PubMed: 41199342
- Original source →
- Free full text: Molecular Brain →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Liu, Y., Sobue, A., Sahara, N., Isobe, M., Tanaka, R., Zhu, Y., et al. (2025). Abnormal behaviors and glial responses in an animal model of tau pathology. Molecular Brain. https://doi.org/10.1186/s13041-025-01252-4
Vancouver
Liu Y, Sobue A, Sahara N, Isobe M, Tanaka R, Zhu Y, et al. Abnormal behaviors and glial responses in an animal model of tau pathology. Molecular Brain. 2025. doi:10.1186/s13041-025-01252-4. PMID: 41199342.
BibTeX
@article{liu2025-41199342,
author = {Liu, Yue and Sobue, Akira and Sahara, Naruhiko and Isobe, Madoka and Tanaka, Rinako and Zhu, Youyun and Zhu, Wenjun and Matsuzaki, Tetsuo and others},
title = {{Abnormal behaviors and glial responses in an animal model of tau pathology}},
journal = {Molecular Brain},
year = {2025},
doi = {10.1186/s13041-025-01252-4},
pmid = {41199342},
url = {https://doi.org/10.1186/s13041-025-01252-4}
}
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