Dataset Information

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

ACCESS DATA

Publications

GABA<sub>A</sub> Receptor-Stabilizing Protein Ubqln1 Affects Hyperexcitability and Epileptogenesis after Traumatic Brain Injury and in a Model of In Vitro Epilepsy in Mice.

Kürten Tabea T Ihbe Natascha N Ueberbach Timo T Distler Ute U Sielaff Malte M Tenzer Stefan S Mittmann Thomas T

International journal of molecular sciences 20220331 7

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 (GABA<sub>A</sub>)-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 GABAergi ...[more]

PMID: 35409261

Similar Datasets

Project description:Warfare has long been associated with traumatic brain injury (TBI) in militarized zones. Common forms of TBI can be caused by a physical insult to the head-brain or by the effects of a high velocity blast shock wave generated by the detonation of an explosive device. While both forms of trauma are distinctly different regarding the mechanism of trauma induction, there are striking similarities in the cognitive and emotional status of survivors. Presently, proven effective therapeutics for the treatment of either form of TBI are unavailable. To be able to develop efficacious therapies, studies involving animal models of physical- and blast-TBI are required to identify possible novel or existing medicines that may be of value in the management of clinical events. We examined indices of cognition and anxiety-like behavior and the hippocampal gene transcriptome of mice subjected to both forms of TBI. We identified common behavioral deficits and gene expression regulations, in addition to unique injury-specific forms of gene regulation. Molecular pathways presented a pattern similar to that seen in gene expression. Interestingly, pathways connected to AlzheimerM-bM-^@M-^Ys disease displayed a markedly different form of regulation depending on the type of TBI. While these data highlight similarities in behavioral outcomes after trauma, the divergence in hippocampal transcriptome observed between models suggests that, at the molecular level, the TBIs are quite different. These models may provide tools to help define therapeutic approaches for the treatment of physical- and blast-TBIs. Based upon observations of increasing numbers of personnel displaying TBI related emotional and behavioral changes in militarized zones, the development of efficacious therapies will become a national if not a global priority. Keywords: Physical-traumatic brain injury; Blast-traumatic brain injury; Cognitive dysfunction; Gene expression; Molecular pathway(s); Neurodegeneration; Stem cells; AlzheimerM-bM-^@M-^Ys disease A mild physical-TBI was induced using a concussive head trauma device described previously (Milman et al., 2005; Zohar et al., 2003). Briefly, mice were lightly anesthetized (Isoflurane) and placed under the weight-drop concussive head trauma instrument. The device consisted of a metal tube (inner diameter 13 mm), placed vertically over the mouse head. A metal weight (30 g) was dropped from the top of the tube (80 cm) and struck the skull at the right side temporal area between the corner of the eye and the ear. A sponge supported the head, allowing some antero-posterior motion without any rotational head movement at the moment of the impact. Experimental conditions used to create a mild low-level blast-TBI and the subsequent model characterization, have been described in detail elsewhere (Rubovitch et al., 2011). In brief, mice were anaesthetized with a combination of ketamine (100 mg/kg) and xylazine (10 mg/kg). Once the animals were fully anaesthetized they were placed at a defined distance from a detonation source, in this case 7 meters. Pressure sensors were used to measure the explosion shock wave pressure (PSI) generated by the detonation (Free-Field ICPM-BM-. Blast Pressure Sensor; PCB Piezoelectronics, Depew, NY, USA, Model 137). At 7 meters from the source of the detonation, the animals were exposed to a maximum of a 2.5 PSI (17.2 kPa) pressure shock wave. Immediately after the induction of the injury, mice were placed back in their cages. Once the animals had recovered from the anesthesia, basic neurological assessments were undertaken to identify any acute neurological dysfunction. Only animals exhibiting no evidence of acute neurological damage post injury were subsequently used in further experiments. Sham treated mouse groups were treated identically; however, they were not exposed to physical- or blast-TBI. Mouse hippocampus tissues were randomly selected from the larger library of samples generated from the behavioral experiments and the numbers utilized in the gene expression study were as follows: sham, n = 5: physical-TBI, n = 4; blast-TBI, n = 7.

Dataset Information

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

Publications

GABA<sub>A</sub> Receptor-Stabilizing Protein Ubqln1 Affects Hyperexcitability and Epileptogenesis after Traumatic Brain Injury and in a Model of In Vitro Epilepsy in Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure