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Authors: Kürten, Tabea
Ihbe, Natascha
Ueberbach, Timo
Distler, Ute
Sielaff, Malte
Tenzer, Stefan
Mittmann, Thomas
Title: GABAA receptor-stabilizing protein Ubqln1 affects hyperexcitability and epileptogenesis after traumatic brain injury and in a model of in vitro epilepsy in mice
Online publication date: 20-Dec-2022
Year of first publication: 2022
Language: english
Abstract: Posttraumatic epilepsy (PTE) is a major public health concern and strongly contributes to human epilepsy cases worldwide. However, an effective treatment and prevention remains a matter of intense research. The present study provides new insights into the gamma aminobutyric acid A (GABAA)-stabilizing protein ubiquilin-1 (ubqln1) and its regulation in mouse models of traumatic brain injury (TBI) and in vitro epilepsy. We performed label-free quantification on isolated cortical GABAergic interneurons from GAD67-GFP mice that received unilateral TBI and discovered reduced expression of ubqln1 24 h post-TBI. To investigate the link between this regulation and the development of epileptiform activity, we further studied ubqln1 expression in hippocampal and cortical slices. Epileptiform events were evoked pharmacologically in acute brain slices by administration of picrotoxin (PTX, 50 μM) and kainic acid (KA, 500 nM) and recorded in the hippocampal CA1 subfield using Multi-electrode Arrays (MEA). Interestingly, quantitative Western blots revealed significant decreases in ubqln1 expression 1–7 h after seizure induction that could be restored by application of the non-selective monoamine oxidase inhibitor nialamide (NM, 10 μM). In picrotoxin-dependent dose–response relationships, NM administration alleviated the frequency and peak amplitude of seizure-like events (SLEs). These findings indicate a role of the monoamine transmitter systems and ubqln1 for cortical network activity during posttraumatic epileptogenesis.
DDC: 540 Chemie
540 Chemistry and allied sciences
570 Biowissenschaften
570 Life sciences
610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
Document type specification: Scientific article
License: CC BY
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Journal: International journal of molecular sciences
Pages or article number: 3902
Publisher: MDPI
Publisher place: Basel
Issue date: 2022
ISSN: 1661-6596
Publisher URL:
Publisher DOI: 10.3390/ijms23073902
Appears in collections:DFG-491381577-G

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