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Spermine inhibits ferroptosis in vascular dementia rats by intervening Nrf2/SLC7A11/GPX4 expression in chondriosome
Wang H, Wang Y, Xie Y, Liu P, Zhao M, Hao R, Zhang H, Li P.. Research Square, 2026-10-09
Topic: Gut, metabolism and diet
Plain-language summary
Background Vascular dementia (VaD) is a major subtype of dementia caused by cerebrovascular disease, with complex pathogenesis involving oxidative stress, calcium dyshomeostasis, and iron-dependent ferroptosis. Excessive reactive oxygen species (ROS) promote Ca 2+ influx via TRPM2 channels, leading to mitochondrial dysfunction and neuronal injury, while iron accumulation accelerates lipid peroxidation. The Nrf2/SLC7A11/GPX4 axis is a key antioxidant pathway that suppresses ferroptosis. Although spermine exhibits neuroprotective properties, its role in VaD and ferroptosis remains insufficiently defined. Methods and Results A modified two-vessel occlusion (2-VO) model was established in Sprague-Dawley rats, followed by spermine administration (150 mg/kg/day). Cognitive function was assessed using the Morris water maze. Histological and ultrastructural changes were evaluated by HE, Nissl staining, and transmission electron microscopy. Oxidative stress markers (ROS, MDA, GSH, SOD, Fe 2+ ) and protein expression (TRPM2, Nrf2, SLC7A11, GPX4) were analyzed by biochemical assays, Western blot, immunohistochemistry, and immunofluorescence. In vitro, SH-SY5Y cells subjected to OGD/R were treated with spermidine (1.4 µg/mL). VaD rats and OGD/R-treated cells exhibited cognitive deficits, neuronal damage, mitochondrial dysfunction, increased TRPM2 expression, decreased Nrf2/SLC7A11/GPX4 levels, and enhanced oxidative stress and ferroptosis. Spermine significantly improved cognitive performance, alleviated neuronal and mitochondrial injury, suppressed TRPM2 expression, restored Nrf2/SLC7A11/GPX4 signaling, and reduced oxidative stress and ferroptosis. Conclusion Spermine exerts neuroprotective effects in VaD by inhibiting TRPM2-mediated oxidative stress and activating the Nrf2/SLC7A11/GPX4 pathway, thereby suppressing ferroptosis. These findings highlight spermine as a promising therapeutic candidate targeting ferroptosis in vascular dementia.
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APA 7th
Wang, H., Wang, Y., Xie, Y., Liu, P., Zhao, M., Hao, R., et al. (2026). Spermine inhibits ferroptosis in vascular dementia rats by intervening Nrf2/SLC7A11/GPX4 expression in chondriosome. Research Square. https://doi.org/10.21203/rs.3.rs-11156074/v1
Vancouver
Wang H, Wang Y, Xie Y, Liu P, Zhao M, Hao R, et al. Spermine inhibits ferroptosis in vascular dementia rats by intervening Nrf2/SLC7A11/GPX4 expression in chondriosome. Research Square. 2026. doi:10.21203/rs.3.rs-11156074/v1.
BibTeX
@article{wang2026-88551104,
author = {Wang, H. and Wang, Y. and Xie, Y. and Liu, P. and Zhao, M. and Hao, R. and Zhang, H. and Li, P.},
title = {{Spermine inhibits ferroptosis in vascular dementia rats by intervening Nrf2/SLC7A11/GPX4 expression in chondriosome}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-11156074/v1},
url = {https://doi.org/10.21203/rs.3.rs-11156074/v1}
}
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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Methods and Results A modified two-vessel occlusion (2-VO) model was established in Sprague-Dawley rats, followed by spermine administration (150 mg/kg/day).
- Spermine significantly improved cognitive performance, alleviated neuronal and mitochondrial injury, suppressed TRPM2 expression, restored Nrf2/SLC7A11/GPX4 signaling, and reduced oxidative stress and ferroptosis.
- These findings highlight spermine as a promising therapeutic candidate targeting ferroptosis in vascular dementia.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported and randomized / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | Laboratory or animal study (title names “rats”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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