Single-cell transcriptome analysis reveals dysregulation of microglial iron homeostasis in temporal lobe epilepsy

Zihua He1, Shengyi Liu1, Wenyan Shi1

  • 1Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.

Brain Research
|August 13, 2025
PubMed

Insights

Microglia play a key role in temporal lobe epilepsy (TLE) pathogenesis by dysregulating iron metabolism and causing neuroinflammation. Identifying specific microglial phenotypes offers potential therapeutic targets for drug-resistant epilepsy.

Area of Science:

  • Neuroscience
  • Immunology
  • Genetics

Background:

  • Temporal lobe epilepsy (TLE) is the most common and drug-resistant epilepsy type with an unclear mechanism.
  • Abnormal iron and lipid peroxide accumulation is observed in TLE patient brains.

Purpose of the Study:

  • To investigate the role of microglia in iron metabolism and neuroinflammation in TLE.
  • To identify specific microglial phenotypes associated with TLE pathogenesis.

Main Methods:

  • Analysis of single-cell/single-nucleus RNA sequencing data from TLE patients.
  • Immunohistochemistry and multiplex immunohistochemistry on brain tissues.
  • Gene regulatory network analysis.

Main Results:

  • TLE-associated cells showed increased ferroptosis gene set scores.
  • Microglia in TLE patients exhibited heightened iron accumulation, ferritin synthesis, and oxidative damage, with an inflammatory phenotype.
  • A unique microglial phenotype, similar to Alzheimer's disease-associated microglia, was identified and correlated with seizure frequency.

Conclusions:

  • Microglial dysregulation in iron metabolism and neuroinflammation is critical in TLE pathogenesis.
  • The identified TLE-related microglial phenotype represents a potential therapeutic target for epilepsy.

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