ArticleThe Journal of clinical investigation2025
Multimodal single-cell analyses reveal molecular markers of neuronal senescence in human drug-resistant epilepsy.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Targeted senotherapy improves electrographic and behavioral outcomes in a mouse model of temporal lobe epilepsy.Epilepsia · 2026Article
- Quercetin Mitigates Oxidative Stress-Induced Premature Senescence in SH-SY5Y Neuronal-like Cells.International journal of molecular sciences · 2026Article
- Senescent Cell Clearance Ameliorates Temporal Lobe Epilepsy and Associated Spatial Memory Deficits in Mice.Annals of neurology · 2026Article
- Deciphering epileptogenic and activity-dependent gene programs in the human brain.bioRxiv : the preprint server for biology · 2026Article
- The senescent niche hypothesis: microglial dysfunction and replacement strategies in drug-resistant epilepsy.Frontiers in immunology · 2026Review
- Senolytics as Modulators of Critical Signaling Pathways: a Promising Strategy to Combat Brain Aging and Neurodegenerative Disorders.Molecular neurobiology · 2025Review
- Review
- Zombie neurons in epilepsy: a burgeoning role for senescence in drug-resistant epilepsy.The Journal of clinical investigation · 2025Article
- Metabolic phenotypes: Molecular bridges between health homeostasis and disease imbalance.Computational and structural biotechnology journal · 2025Review
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Authors and funding
28 authors.
Funding
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Abstract
The histopathological neurons in the brain tissue of drug-resistant epilepsy exhibit aberrant cytoarchitecture and imbalanced synaptic circuit function. However, the gene expression changes of these neurons remain unknown, making it difficult to determine the diagnosis or to dissect the mechanism of drug-resistant epilepsy. By integrating whole-cell patch clamp recording and single-cell RNA-seq approaches, we identified a transcriptionally distinct subset of cortical pyramidal neurons. These neurons highly expressed genes CDKN1A (P21), CCL2, and NFKBIA, which associate with mTOR pathway, inflammatory response, and cellular senescence. We confirmed the expression of senescent marker genes in a subpopulation of cortical pyramidal neurons with enlarged soma size in the brain tissue of drug-resistant epilepsy. We further revealed the expression of senescent cell markers P21, P53, COX2, γ-H2AX, and β-Gal, and reduction of nuclear integrity marker Lamin B1 in histopathological neurons in the brain tissue of patients with drug-resistant epilepsy with different pathologies, but not in control brain tissue with no history of epilepsy. Additionally, chronic, but not acute, epileptic seizures induced senescent marker expression in cortical neurons in mouse models of drug-resistant epilepsy. These results provide important molecular markers for histopathological neurons and what we believe to be new insights into the pathophysiological mechanisms of drug-resistant epilepsy.
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