Experimental epileptogenesis in a cell culture model of primary neurons from rat brain: A temporal multi‐scale study

Jablonski J, Hoffmann L, Blümcke I, Fejtová A, Uebe S, Ekici AB, Gnatkovsky V, Kobow K (2021)

Publication Type: Journal article, Original article

Publication year: 2021

Journal

Cells MDPI

Book Volume: 10

Article Number: 3004

Journal Issue: 11

DOI: 10.3390/cells10113004

Open Access Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616120/

Abstract

Understanding seizure development requires an integrated knowledge of different scales of organization of epileptic networks. We developed a model of “epilepsy‐in‐a‐dish” based on dissociated primary neuronal cells from neonatal rat hippocampus. We demonstrate how a single application of glutamate stimulated neurons to generate spontaneous synchronous spiking activity with further progression into spontaneous seizure‐like events after a distinct latency period. By computational analysis, we compared the observed neuronal activity in vitro with intracranial electroencephalography (EEG) data recorded from epilepsy patients and identified strong similarities, including a related sequence of events with defined onset, progression, and termination. Next, a link between the neurophysiological changes with network composition and cellular structure down to molecular changes was established. Temporal development of epileptiform network activity correlated with increased neurite outgrowth and altered branching, increased ratio of glutamatergic over GABAergic synapses, and loss of calbindin‐positive interneurons, as well as genome‐wide alterations in DNA methylation. Differentially methylated genes were engaged in various cellular activities related to cellular structure, intracellular signaling, and regulation of gene expression. Our data provide evidence that a single short‐term excess of glutamate is sufficient to induce a cascade of events covering different scales from molecule‐ to network‐level, all of which jointly contribute to seizure development.

Authors with CRIS profile

Janos Jablonski Lehrstuhl für Neuropathologie Ingmar Blümcke Lehrstuhl für Neuropathologie Anna Fejtová Professur für Molekulare Psychiatrie Steffen Uebe Institute of Human Genetics Arif Bülent Ekici Institute of Human Genetics Katja Kobow Institute of Neuropathology

Involved external institutions

Universitätsklinikum Bonn DE Germany (DE)

How to cite

APA:

Jablonski, J., Hoffmann, L., Blümcke, I., Fejtová, A., Uebe, S., Ekici, A.B.,... Kobow, K. (2021). Experimental epileptogenesis in a cell culture model of primary neurons from rat brain: A temporal multi‐scale study. Cells, 10(11). https://doi.org/10.3390/cells10113004

MLA:

Jablonski, Janos, et al. "Experimental epileptogenesis in a cell culture model of primary neurons from rat brain: A temporal multi‐scale study." Cells 10.11 (2021).

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