Autoren:	Kürten, Tabea Ihbe, Natascha Ueberbach, Timo Distler, Ute Sielaff, Malte Tenzer, Stefan Mittmann, Thomas
Titel:	GABAA receptor-stabilizing protein Ubqln1 affects hyperexcitability and epileptogenesis after traumatic brain injury and in a model of in vitro epilepsy in mice
Online-Publikationsdatum:	20-Dez-2022
Erscheinungsdatum:	2022
Sprache des Dokuments:	Englisch
Zusammenfassung/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-Sachgruppe:	540 Chemie 540 Chemistry and allied sciences 570 Biowissenschaften 570 Life sciences 610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7028
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Weitere Angaben zur Dokumentart:	Scientific article
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	International journal of molecular sciences 23 7
Seitenzahl oder Artikelnummer:	3902
Verlag:	MDPI
Verlagsort:	Basel
Erscheinungsdatum:	2022
ISSN:	1661-6596 1422-0067
URL der Originalveröffentlichung:	https://doi.org/10.3390/ijms23073902
DOI der Originalveröffentlichung:	10.3390/ijms23073902
Enthalten in den Sammlungen:	DFG-491381577-G