Evidence map›Paper›PMID 42881408›Full record

ArticleJournal of translational medicine2026

Single-nucleus transcriptomic analysis reveals subfield-specific cell-to-cell synaptic reorganisation of the mouse hippocampus in focal temporal lobe epilepsy.

Javier Villegas-Salmerón, Albert Sanfeliu, Omar Mamad, Toby Segasby, Janosch P Heller, Petra Bencúrová, Niamh M C Connolly, David C Henshall

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Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Javier Villegas-SalmerónResearch Ireland Centre for Research Training in Genomics Data Science, Dublin, Ireland.
Albert SanfeliuFutureNeuro Research Ireland Centre for Translational Brain Science, RCSI University of Medicine & Health Sciences, Dublin, D02 YN77, Ireland.
Omar MamadFutureNeuro Research Ireland Centre for Translational Brain Science, RCSI University of Medicine & Health Sciences, Dublin, D02 YN77, Ireland.
Toby SegasbyFutureNeuro Research Ireland Centre for Translational Brain Science, RCSI University of Medicine & Health Sciences, Dublin, D02 YN77, Ireland.
Janosch P HellerDCU Life Sciences Institute, Dublin City University, Dublin 9, Ireland.
Petra BencúrováFutureNeuro Research Ireland Centre for Translational Brain Science, RCSI University of Medicine & Health Sciences, Dublin, D02 YN77, Ireland.
Niamh M C Connolly *FutureNeuro Research Ireland Centre for Translational Brain Science, RCSI University of Medicine & Health Sciences, Dublin, D02 YN77, Ireland.
David C Henshall *FutureNeuro Research Ireland Centre for Translational Brain Science, RCSI University of Medicine & Health Sciences, Dublin, D02 YN77, Ireland. dhenshall@rcsi.ie.ORCID http://orcid.org/0000-0001-6237-9632

Funding

Research Ireland 18/CRT/6214Research Ireland 18/RI/5723Research Ireland 21/RC/10294_P2Research Ireland IRCLA/2022/3828
6 · The paper itself

Abstract

backgroundPreclinical animal models are critical tools to study the pathophysiology of epilepsy. The intra-amygdala microinjection of kainic acid in mice recapitulates key features of drug-resistant temporal lobe epilepsy, including unilateral hippocampal pathology and broad resistance to anti-seizure medicines, and is increasingly used to discover novel targets for disease-modification. Defining the gene expression landscape at single-cell resolution may reveal how different cell types adapt to chronic seizures and help identify additional biomarkers and targets in this model.

methodsWe generated a single-nucleus RNA-seq dataset using ipsilateral hippocampi collected two weeks after status epilepticus in the mouse intra-amygdala kainic acid model. Samples from epileptic and control mice were processed using the 10X Genomics platform, with a total of 34,737 nuclei sequenced representing all major cellular subtypes in the hippocampus.

resultsDifferential gene expression analysis revealed cell subtype- and subfield-specific dysregulation across the hippocampus in epileptic mice. Activity-regulated genes were increased in neurons in the dentate gyrus, CA1 and CA3 subfields. Dentate gyrus neurons displayed the greatest differential gene expression, enriched for synaptogenesis, plasticity and NMDA receptor signalling. Transcription profiles for CA3 glutamatergic neurons indicated mechanical and injury responses whereas CA1 signatures were enriched for neuroinflammation and wound healing. Astrocytes displayed the most differential gene expression among glial populations, characterised by mixed reactive pro- and anti-inflammatory responses and altered metabolic states. Cell-cell communication analysis predicted extensive remodelling of hippocampal signalling across cell subtypes, including for glutamate and latrophilin-mediated ligand-receptor pairing among dentate gyrus and CA2 neuron connections.

conclusionsOur study provides an atlas of transcriptomic changes at the single cell level for the mouse intra-amygdala kainic acid model of temporal lobe epilepsy, highlighting network adaptations to hyperexcitability. The findings support a cell subtype basis for gene expression changes underlying pathophysiology and can guide novel therapeutic strategies to reduce or reverse chronic neuronal hyperexcitability in drug-resistant epilepsy.

Indexed as

Cell NucleusEpilepsy, Temporal LobeGene Expression ProfilingHippocampusSynapsesTranscriptomeAnimalsGene Expression RegulationKainic AcidMaleMiceMice, Inbred C57BLNeuronsKainic AcidHippocampusIntercellular communicationIntra-amygdala kainic acid modelLatrophilin signallingSingle-nucleus RNA-seqTemporal lobe epilepsy

Identifiers

PMID42881408
PMCPMC13670734

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