LFQ proteomics of isolated GABAergic interneurons from mouse models of traumatic brain injury

ABSTRACT: Posttraumatic epilepsy (PTE) is a major public health concern and strongly contributes to human epilepsy cases worldwide. However, their effective treatment and prevention remains a matter of intense research. The present study provides new insights into the GABAA-receptor-stabilizing protein ubiquilin-1 (ubqln1) and its regulation in a mouse model 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 hours post-TBI. To investigate the link between this regulation and the development of epileptiform activity, we further studied the ubqln1 expression in hippocampal and cortical slices. Epileptiform events were evoked pharmacologically in acute brain slices by administration of picrotoxin (50 μM) and kainic acid (500 nM) and recorded in the hippocampal CA1 region using Multielectrode Arrays (MEA). Interestingly, quantitative Western blots revealed significant decreases in the ubqln1 expression 1-7 hours after seizure induction that could be restored by the application of the non-selective monoamine oxidase inhibitor nialamide (NM, 10 μM). In picrotoxin-dependent dose-response relationships, NM-administration alleviated frequency and peak amplitude of SLEs. These findings indicate a potential role of the monoamine transmitter systems in recovering excitatory-inhibitory (E/I) balance in posttraumatic epileptogenesis.

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Stefan Tenzer 

PROVIDER: PXD031368 | JPOST Repository | Thu Jul 14 00:00:00 BST 2022

REPOSITORIES: jPOST