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Senescent Cell Clearance Ameliorates Temporal Lobe Epilepsy and Associated Spatial Memory Deficits in Mice
Tahiyana Khan1,2, David J McFall1,2, Abbas I Hussain2
1Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA.
Annals of Neurology
|December 22, 2025
Summary
Cellular senescence, a marker of aging cells, is elevated in temporal lobe epilepsy (TLE). Clearing these senescent cells (SCs) in mice reduced seizures and improved cognitive function, suggesting a new therapeutic target for TLE.
Area of Science:
- Neuroscience
- Cellular Biology
- Epilepsy Research
Background:
- Temporal lobe epilepsy (TLE) treatment focuses on symptomatic control, lacking disease-modifying strategies.
- Cellular senescence is implicated in neurodegeneration but its role in TLE remains unexplored.
Purpose of the Study:
- Investigate the role of cellular senescence in TLE.
- Determine if senescent cell clearance can ameliorate TLE pathology and symptoms.
Main Methods:
- Analyzed senescent cell markers in human TLE hippocampi using multiplexed immunofluorescence.
- Utilized a pilocarpine-induced mouse model of TLE for immunohistochemistry, behavioral tests, and EEG.
- Employed genetic and pharmacological (dasatinib/quercetin) senolysis to remove senescent cells.
Main Results:
- Human TLE cases showed a 5-fold increase in senescent glia compared to controls.
- Senescence markers increased in mice post-status epilepticus, primarily in microglia.
- Senolytic treatment reduced senescent cells by 50%, improved synaptic plasticity and memory, and decreased seizure frequency.
Conclusions:
- Senescent cells accumulate in human TLE and a TLE mouse model.
- Targeted clearance of senescent cells offers a potential therapeutic strategy for TLE and its cognitive comorbidities.
