Gutenberg Open Science: GABAA receptor-stabilizing protein Ubqln1 affects hyperexcitability and epileptogenesis after traumatic brain injury and in a model of in vitro epilepsy in mice

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7028

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DC Field	Value	Language
dc.contributor.author	Kürten, Tabea	-
dc.contributor.author	Ihbe, Natascha	-
dc.contributor.author	Ueberbach, Timo	-
dc.contributor.author	Distler, Ute	-
dc.contributor.author	Sielaff, Malte	-
dc.contributor.author	Tenzer, Stefan	-
dc.contributor.author	Mittmann, Thomas	-
dc.date.accessioned	2022-12-20T12:06:12Z	-
dc.date.available	2022-12-20T12:06:12Z	-
dc.date.issued	2022	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/7042	-
dc.description.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.	en_GB
dc.description.sponsorship	Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 491381577	de
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	540 Chemie	de_DE
dc.subject.ddc	540 Chemistry and allied sciences	en_GB
dc.subject.ddc	570 Biowissenschaften	de_DE
dc.subject.ddc	570 Life sciences	en_GB
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	GABAA receptor-stabilizing protein Ubqln1 affects hyperexcitability and epileptogenesis after traumatic brain injury and in a model of in vitro epilepsy in mice	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-7028	-
jgu.type.contenttype	Scientific article	de
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	International journal of molecular sciences	de
jgu.journal.volume	23	de
jgu.journal.issue	7	de
jgu.pages.alternative	3902	de
jgu.publisher.year	2022	-
jgu.publisher.name	MDPI	de
jgu.publisher.place	Basel	de
jgu.publisher.uri	https://doi.org/10.3390/ijms23073902	de
jgu.publisher.issn	1661-6596	de
jgu.publisher.issn	1422-0067	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	540	de
jgu.subject.ddccode	570	de
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.3390/ijms23073902	de
jgu.organisation.ror	https://ror.org/023b0x485	-
jgu.subject.dfg	Naturwissenschaften	de
Appears in collections:	DFG-491381577-G

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