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Mitochondrial Reactive Oxygen Species Production in Vascular Dementia Following Experimental Diabetes
Ed Wilson Santos, Subika Khatoon, Yun‐Min Zheng, Yong-Xiao Wang. Cells, 2025-08-15
Topic: Brain proteins, microglia and lab models
Type 1 diabetes (T1D) is a serious disease which affects millions of people worldwide and is a major factor for vascular contributions to cognitive impairment and dementia (VCID). In this study, we first characterized cognitive and memory impairments, then evaluated their underlying molecular mechanisms, and finally determined sex-dependent effects in male and female mice with streptozotocin (STZ)-induced T1D. Our findings indicated that significant cognitive impairment, memory loss, and vascular dementia occurred in male and female T1D mice. Cerebral artery (CA) blood flow was greatly reduced in the various brain regions tested. ROS generation in isolated cells, mitochondria, and mitochondrial complex III from CA smooth muscle cells (CASMCs) were all increased in T1D. DNA damage and Tau phosphorylation in CASMCs were largely increased. Linear regression analysis revealed that T1D-induced increased blood glucose was highly correlated with increased ROS production and increased VCID. Taken together, we conclude that T1D causes increased mitochondrial complex III ROS production, DNA damage, and Chk2 phosphorylation in CASMC, thereby leading to vascular dementia in both male and female mice; our results further demonstrate that mitochondrial complex III ROS-mediated DNA damage is more significant in male than female mice, which contributes to more serious vascular dementia in the former than the latter.
Key findings
- Our findings indicated that significant cognitive impairment, memory loss, and vascular dementia occurred in male and female T1D mice.
- Linear regression analysis revealed that T1D-induced increased blood glucose was highly correlated with increased ROS production and increased VCID.
- Taken together, we conclude that T1D causes increased mitochondrial complex III ROS production, DNA damage, and Chk2 phosphorylation in CASMC, thereby leading to vascular dementia in both male and female mice; our results further demonstrate that mitochondrial complex III ROS-mediated DNA damage is more significant in male than female mice, which contributes to more serious vascular dementia in the former than the latter.
Why it matters
In mice with diabetes, this study found that increased reactive oxygen species from mitochondria in brain artery cells led to DNA damage and vascular dementia in both males and females. The results suggest that targeting this process might help prevent vascular dementia related to diabetes, but this is early animal research and not yet tested in people.
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Study details
- Evidence strengthLow
How this study scored 35/100
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. We have no data on senior author's track record, so that was left out: it earned 34 of the 96 points we could judge it on, which is 35 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cells) |
| Journal's citation record | 2 / 4 | Cells: journal h-index 234 (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 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.5× 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 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Yong-Xiao Wang holds only 7 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 0 / 3 | Albany Medical College: institution h-index 411 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40862739) |
| Free to read | 2 / 2 | Free to read |
| Points | 34 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 34 of the 96 points we could judge it on is 35 out of 100. |
| Total | 35 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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. Check the citation against the original before you use it.
APA 7th
Santos, E. W., Khatoon, S., Zheng, Y., & Wang, Y.-X. (2025). Mitochondrial Reactive Oxygen Species Production in Vascular Dementia Following Experimental Diabetes. Cells. https://doi.org/10.3390/cells14161260
Vancouver
Santos EW, Khatoon S, Zheng Y, Wang Y.-X. Mitochondrial Reactive Oxygen Species Production in Vascular Dementia Following Experimental Diabetes. Cells. 2025. doi:10.3390/cells14161260. PMID: 40862739.
BibTeX
@article{santos2025-40862739,
author = {Santos, Ed Wilson and Khatoon, Subika and Zheng, Yun‐Min and Wang, Yong-Xiao},
title = {{Mitochondrial Reactive Oxygen Species Production in Vascular Dementia Following Experimental Diabetes}},
journal = {Cells},
year = {2025},
doi = {10.3390/cells14161260},
pmid = {40862739},
url = {https://doi.org/10.3390/cells14161260}
}
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