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Lookup NU author(s): Neela Codadu, Dr Simon CockellORCiD, Professor Andrew Trevelyan, Dr Ryley Parrish
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 Vaughan et al. Seizures are generally associated with epilepsy but may also be a symptom of many other neurological conditions. A hallmark of a seizure is the intensity of the local neuronal activation, which can drive large-scale gene transcription changes. Such changes in the transcriptional profile likely alter neuronal function, thereby contributing to the pathological process. Therefore, there is a strong clinical imperative to characterize how gene expression is changed by seizure activity. To this end, we developed a simplified ex vivo technique for studying sei-zure-induced transcriptional changes. We compared the RNA sequencing profile in mouse neocor-tical tissue with up to 3 h of epileptiform activity induced by 4-aminopyridine (4AP) relative to control brain slices not exposed to the drug. We identified over 100 genes with significantly altered expression after 4AP treatment, including multiple genes involved in MAPK, TNF, and neuroinflammatory signaling pathways, all of which have been linked to epilepsy previously. Notably, the patterns in male and female brain slices were almost identical. Various immediate early genes were among those showing the largest upregulation. The set of down-regulated genes included ones that might be expected either to increase or to decrease neuronal excitability. In summary, we found the seizure-induced transcriptional profile complex, but the changes aligned well with an analysis of published epilepsy-associated genes. We discuss how simple models may provide new angles for investigating seizure-induced transcriptional changes.
Author(s): Vaughan AJ, McMeekin LJ, Hine K, Stubbs IW, Codadu NK, Cockell S, Hill JT, Cowell R, Trevelyan AJ, Parrish RR
Publication type: Article
Publication status: Published
Journal: eNeuro
Year: 2024
Volume: 11
Issue: 5
Print publication date: 01/05/2024
Online publication date: 25/04/2024
Acceptance date: 18/04/2024
Date deposited: 03/06/2024
ISSN (electronic): 2373-2822
Publisher: Society for Neuroscience
URL: https://doi.org/10.1523/ENEURO.0520-23.2024
DOI: 10.1523/ENEURO.0520-23.2024
PubMed id: 38664009
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