Single-cell transcriptome analysis reveals dysregulation of microglial iron homeostasis in temporal lobe epilepsy
Zihua He, Shengyi Liu, Wenyan Shi, Yi Yang, Jierui Wang, Jiaqi Wang, Jianqiong Yin, Sisi Shen et al.. Brain research, 2025-08-11
Topic: Inflammation, microglia and astrocytes
Temporal lobe epilepsy (TLE) is the most common and drug-resistant type of epilepsy with an unknown mechanism. Abnormal accumulation of iron and lipid peroxides in the brain of TLE patients has been demonstrated. In this study, we investigated the role of microglia in iron metabolism and neuroinflammation by systematically analyzing single-cell/single-nucleus RNA sequencing data from TLE patients. Our results showed that cells associated with TLE phenotype were significantly increased in the ferroptosis gene set score and positive expression of ACSL4 and 4-HNE was observed by immunohistochemistry in brain tissues of TLE patients. Compared to the control group, microglia in the TLE group exhibited heightened metabolic activity in iron accumulation, ferritin synthesis, and oxidative damage, manifesting an inflammation-related phenotype and secreting multiple inflammatory factors. Furthermore, we discovered a unique microglial phenotype characterized by iron accumulation and neuroinflammation, resembling microglia associated with Alzheimer's disease. The abundance of these microglial cells showed significant differences between TLE patients with high and low seizure frequencies and correlated positively with seizure frequency. Gene regulatory network analysis further revealed an enrichment of inflammation and oxidative stress-related transcription factors in these cells. Additionally, we identified a TLE-related gene co-expression module whose transcriptional characterization highly correlate with these distinct microglia. Multiplex immunohistochemistry validated the expression of these cellular marker genes in brain tissues of TLE patients. In summary, these findings underscore the critical role of microglial dysregulation in iron metabolism and neuroinflammation in the pathogenesis of TLE. By identifying a specific microglial phenotype, our research suggests a potential target for developing new therapeutic strategies for TLE.
Key findings
- Abnormal accumulation of iron and lipid peroxides in the brain of TLE patients has been demonstrated.
- Our results showed that cells associated with TLE phenotype were significantly increased in the ferroptosis gene set score and positive expression of ACSL4 and 4-HNE was observed by immunohistochemistry in brain tissues of TLE patients.
- Compared to the control group, microglia in the TLE group exhibited heightened metabolic activity in iron accumulation, ferritin synthesis, and oxidative damage, manifesting an inflammation-related phenotype and secreting multiple inflammatory factors.
- Furthermore, we discovered a unique microglial phenotype characterized by iron accumulation and neuroinflammation, resembling microglia associated with Alzheimer's disease.
- The abundance of these microglial cells showed significant differences between TLE patients with high and low seizure frequencies and correlated positively with seizure frequency.
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Study details
- Evidence strengthLow
How this study scored 43/100
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 journal's citation record, 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, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Brain research) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | — / 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40803604) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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APA 7th
He, Z., Liu, S., Shi, W., Yang, Y., Wang, J., Wang, J., et al. (2025). Single-cell transcriptome analysis reveals dysregulation of microglial iron homeostasis in temporal lobe epilepsy. Brain research. https://doi.org/10.1016/j.brainres.2025.149885
Vancouver
He Z, Liu S, Shi W, Yang Y, Wang J, Wang J, et al. Single-cell transcriptome analysis reveals dysregulation of microglial iron homeostasis in temporal lobe epilepsy. Brain research. 2025. doi:10.1016/j.brainres.2025.149885. PMID: 40803604.
BibTeX
@article{he2025-40803604,
author = {He, Zihua and Liu, Shengyi and Shi, Wenyan and Yang, Yi and Wang, Jierui and Wang, Jiaqi and Yin, Jianqiong and Shen, Sisi and others},
title = {{Single-cell transcriptome analysis reveals dysregulation of microglial iron homeostasis in temporal lobe epilepsy}},
journal = {Brain research},
year = {2025},
doi = {10.1016/j.brainres.2025.149885},
pmid = {40803604},
url = {https://doi.org/10.1016/j.brainres.2025.149885}
}
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