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Exercise-induced irisin ameliorates cognitive impairment following chronic cerebral hypoperfusion by suppressing neuroinflammation and hippocampal neuronal apoptosis
Weiping Xiao, Yibing Yang, Bai Lu, Peixuan Yang, Runze Li, Daizhi Yang, Fanying Li, Lingzhi Quan et al.. Journal of Neuroinflammation, 2025-06-28
Topic: Brain proteins, microglia and lab models
Hippocampal and serum irisin levels were progressively reduced in CCH mice. Additionally, expression of integrins αV and β5 in hippocampal neurons, microglia, and astrocytes decreased post-CCH. FAE effectively enhanced both peripheral and central irisin expression. Increased endogenous irisin levels inhibited CCH-induced hippocampal neuronal apoptosis and microglial activation, thereby promoting neuronal survival and partially ameliorating white matter injury. These changes led to improvements in memory, motor function, and anxiety- and depression-like behaviors. Mechanistically, the neuroprotective effects of irisin were mediated by enhanced hippocampal neuronal and microglial autophagy through increased AMPK phosphorylation and decreased mTOR phosphorylation-effects abolished by CT treatment. Our findings demonstrate that enhancing endogenous irisin via FAE mitigates CCH-induced neuronal apoptosis, microglial activation, cognitive impairment, and affective behavioral deficits by promoting autophagy through the integrin αVβ5/AMPK/mTOR signaling pathway.
Key findings
- Hippocampal and serum irisin levels were progressively reduced in CCH mice.
- Additionally, expression of integrins αV and β5 in hippocampal neurons, microglia, and astrocytes decreased post-CCH.
- FAE effectively enhanced both peripheral and central irisin expression.
- Increased endogenous irisin levels inhibited CCH-induced hippocampal neuronal apoptosis and microglial activation, thereby promoting neuronal survival and partially ameliorating white matter injury.
- These changes led to improvements in memory, motor function, and anxiety- and depression-like behaviors.
Why it matters
In mice with chronic reduced brain blood flow, exercise-induced irisin reduced neuroinflammation and hippocampal neuron death and improved memory and behavior through the integrin αVβ5/AMPK/mTOR pathway. These findings are in animals and do not yet show that irisin or exercise treats cognitive impairment in people.
Study details
- Participants212
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Neuroinflammation) |
| Journal's citation record | 2 / 4 | Journal of Neuroinflammation: journal h-index 216 (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 | 2 / 4 | 212 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 25 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 7.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 25 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Liang Feng: h-index 15 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Sun Yat-sen University: institution h-index 851 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40581647) |
| Free to read | 2 / 2 | Free to read |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s12974-025-03493-5
- PubMed: 40581647
- Original source →
- Free full text: Journal of Neuroinflammation →
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
Xiao, W., Yang, Y., Lu, B., Yang, P., Li, R., Yang, D., et al. (2025). Exercise-induced irisin ameliorates cognitive impairment following chronic cerebral hypoperfusion by suppressing neuroinflammation and hippocampal neuronal apoptosis. Journal of Neuroinflammation. https://doi.org/10.1186/s12974-025-03493-5
Vancouver
Xiao W, Yang Y, Lu B, Yang P, Li R, Yang D, et al. Exercise-induced irisin ameliorates cognitive impairment following chronic cerebral hypoperfusion by suppressing neuroinflammation and hippocampal neuronal apoptosis. Journal of Neuroinflammation. 2025. doi:10.1186/s12974-025-03493-5. PMID: 40581647.
BibTeX
@article{xiao2025-40581647,
author = {Xiao, Weiping and Yang, Yibing and Lu, Bai and Yang, Peixuan and Li, Runze and Yang, Daizhi and Li, Fanying and Quan, Lingzhi and others},
title = {{Exercise-induced irisin ameliorates cognitive impairment following chronic cerebral hypoperfusion by suppressing neuroinflammation and hippocampal neuronal apoptosis}},
journal = {Journal of Neuroinflammation},
year = {2025},
doi = {10.1186/s12974-025-03493-5},
pmid = {40581647},
url = {https://doi.org/10.1186/s12974-025-03493-5}
}
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