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Muscone enhances synaptic function in vascular dementia through activating BDNF-TrkB-NP2 signaling pathway
Ping Huang, Hao Sun, Yuang Chen, Jiacheng Li, Yuqin Peng, Chaowen Ge, Kai Zhu, Xian Zhou et al.. International Immunopharmacology, 2025-02-08
Topic: Brain proteins, microglia and lab models
• To clarify the key role of Muscone delayed the development of vascular dementia (VD). • To reveal synaptic function in VD associated with neuronal pentraxin receptor (NP2). • To reveal that Muscone alleviates VD through the BDNF-TrkB-NP2 signaling pathway initially. The objective of this study is to explore the mechanism by which Muscone treats VD. Cognitive function was evaluated by behavioral tests, cerebral blood flow(CBF) was detected with laser speckle imaging(LSI) on rat model induced by bilateral common carotid artery ligation(2-VO). To further elucidate the mechanism of Muscone acts on synaptic function, Mendelian randomization test was employed to identify neuronal pentraxin receptor (NPTXR) as a risk factor for VD. Subsequently, Oxygen and Glucose-Deprivation/Reoxygenation (OGD/R) model was established in HT22 cells. BDNF transfection, protein docking, and co-immunoprecipitation were utilized to validate whether the protective effect of Muscone is mediated through regulation of the BDNF-TrkB-NP2 pathway. Muscone significantly enhanced the cognitive performance, memory capacity in rats, promoted axonal growth and increased dendritic spine density. Muscone effectively improved cell survival rates, mitigated the accumulation of ROS and Ca 2+ following OGD/R treatment. Furthermore, Muscone led to a significant upregulation of synapse-associated proteins expression. Importantly, Muscone exhibited a notable ability to elevate BDNF levels, with subsequent binding with its downstream molecule TrkB to NP2. The activation of the BDNF-TrkB-NP2 pathway and synaptic function enhancement by Muscone contribute to its protective effect against VD injury. Therefore, our study uncovers a novel mechanism underlying the anti-VD properties of Muscone.
Key findings
- • To clarify the key role of Muscone delayed the development of vascular dementia (VD). • To reveal synaptic function in VD associated with neuronal pentraxin receptor (NP2). • To reveal that Muscone alleviates VD through the BDNF-TrkB-NP2 signaling pathway initially.
- Muscone significantly enhanced the cognitive performance, memory capacity in rats, promoted axonal growth and increased dendritic spine density.
- Furthermore, Muscone led to a significant upregulation of synapse-associated proteins expression.
Why it matters
In a rat model of vascular dementia and in HT22 cells, Muscone improved cognitive performance and synaptic measures via the BDNF-TrkB-NP2 pathway. These are animal and cell findings and do not yet show a treatment, cure or prevention in people.
Study details
- Evidence strengthLow
How this study scored 37/100
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 (International Immunopharmacology) |
| Journal's citation record | 2 / 4 | International Immunopharmacology: journal h-index 165 (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 | 2 / 7 | Cited 9 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.7× 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 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Ning Wang: h-index 19 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Western Sydney University: institution h-index 499 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39923578) |
| Free to read | 2 / 2 | Free to read |
| Total | 37 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.intimp.2025.114232
- PubMed: 39923578
- Original source →
- Free full text: International Immunopharmacology →
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
Huang, P., Sun, H., Chen, Y., Li, J., Peng, Y., Ge, C., et al. (2025). Muscone enhances synaptic function in vascular dementia through activating BDNF-TrkB-NP2 signaling pathway. International Immunopharmacology. https://doi.org/10.1016/j.intimp.2025.114232
Vancouver
Huang P, Sun H, Chen Y, Li J, Peng Y, Ge C, et al. Muscone enhances synaptic function in vascular dementia through activating BDNF-TrkB-NP2 signaling pathway. International Immunopharmacology. 2025. doi:10.1016/j.intimp.2025.114232. PMID: 39923578.
BibTeX
@article{huang2025-39923578,
author = {Huang, Ping and Sun, Hao and Chen, Yuang and Li, Jiacheng and Peng, Yuqin and Ge, Chaowen and Zhu, Kai and Zhou, Xian and others},
title = {{Muscone enhances synaptic function in vascular dementia through activating BDNF-TrkB-NP2 signaling pathway}},
journal = {International Immunopharmacology},
year = {2025},
doi = {10.1016/j.intimp.2025.114232},
pmid = {39923578},
url = {https://doi.org/10.1016/j.intimp.2025.114232}
}
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