Molecular and neurochemical substrates of the audiogenic seizure strains: The GASH:Sal model

Prieto-Martín, Ana I.; Aroca-Aguilar, José-Daniel; Sánchez-Sánchez, Francisco; Muñoz, Luis J.; López, Dolores E.; Escribano, Julio; Cabo, Carlos de

doi:10.1016/j.yebeh.2015.05.025

Cited by 28 publications

(24 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Other animal models of audiogenic epilepsy generated by artificial selection include the GAERS [19], the WAG/Rij [20] and the WAR [23], in which an auditory stimulus triggers the onset of audiogenic seizures. In all these models, different types of studies on seizures and pharmacological treatments have been conducted in the inferior colliculus as an epileptogenic nucleus and in auditory pathways [31,[74][75][76][77][78]. In the GASH/Sal model, previous studies have determined that susceptibility to developing the epileptic phenotype shows an autosomal recessive inheritance pattern [24].…”

Section: Plos Onementioning

confidence: 99%

Analysis of gene variants in the GASH/Sal model of epilepsy

et al. 2020

Self Cite

View full text Add to dashboard Cite

Epilepsy is a complex neurological disorder characterized by sudden and recurrent seizures, which are caused by various factors, including genetic abnormalities. Several animal models of epilepsy mimic the different symptoms of this disorder. In particular, the genetic audiogenic seizure hamster from Salamanca (GASH/Sal) animals exhibit sound-induced seizures similar to the generalized tonic seizures observed in epileptic patients. However, the genetic alterations underlying the audiogenic seizure susceptibility of the GASH/Sal model remain unknown. In addition, gene variations in the GASH/Sal might have a close resemblance with those described in humans with epilepsy, which is a prerequisite for any new preclinical studies that target genetic abnormalities. Here, we performed whole exome sequencing (WES) in GASH/Sal animals and their corresponding controls to identify and characterize the mutational landscape of the GASH/Sal strain. After filtering the results, moderate-and high-impact variants were validated by Sanger sequencing, assessing the possible impact of the mutations by "in silico" reconstruction of the encoded proteins and analyzing their corresponding biological pathways. Lastly, we quantified gene expression levels by RT-qPCR. In the GASH/Sal model, WES showed the presence of 342 variations, in which 21 were classified as high-impact mutations. After a full bioinformatics analysis to highlight the high quality and reliable variants, the presence of 3 high-impact and 15 moderate-impact variants were identified. Gene expression analysis of the high-impact variants of Asb14 (ankyrin repeat and SOCS Box Containing 14), Msh3 (MutS Homolog 3) and Arh-gef38 (Rho Guanine Nucleotide Exchange Factor 38) genes showed a higher expression in the GASH/Sal than in control hamsters. In silico analysis of the functional consequences indicated that those mutations in the three encoded proteins would have severe functional alterations. By functional analysis of the variants, we detected 44 significantly enriched pathways, including the glutamatergic synapse pathway. The data show three high-impact mutations with a major impact on the function of the proteins encoded by these genes, although no mutation in these three genes has been associated with some type of epilepsy until now. Furthermore, GASH/Sal animals also showed gene variants associated with different types of epilepsy that has been extensively documented, as well as mutations in other genes that PLOS ONE PLOS ONE | https://doi.

show abstract

Section: Plos Onementioning

confidence: 99%

Analysis of gene variants in the GASH/Sal model of epilepsy

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…In recent years, the idea is gaining strength that impairment of the inhibitory systems could be at the root of epileptic seizures [1]. More specifically, a crucial role has been proposed for interneurons secreting γ-Aminobutyric acid (GABA) as their primary neurotransmitter [2][3][4]. GABA amino acid neurotransmitter is responsible for most of the fast-inhibitory neurotransmission in the brain by acting on its putative ionotropic receptors type A (GABA A R).…”

mentioning

confidence: 99%

“…This exchange in NKCC1 / KCC2 expression leads to higher Cl -levels inside the neuron and therefore GABA binding to GABA A Rs results in membrane depolarization during the neonatal stages [5][6][7]. Interestingly, alterations in NKCC1 / KCC2 balance have also been described in epilepsy, both in patients and animal models [4,[8][9][10][11][12][13][14]. This evidence has led to the hypothesis that an imbalance in the expression of these cotransporters may be at the origin of various types of epilepsies and could be considered as new therapeutical targets.…”

mentioning

confidence: 99%

From nephron to neuron: an exciting journey in search of a cure for epilepsy

Cabo¹

2017

Brain Nerves

Self Cite

View full text Add to dashboard Cite

“…Although the data were obtained as well which demonstrated the influence of this drug on metabotropic GABA-B receptor [22] . It is the common knowledge that AE is determined (at least partly) by the excitatory and inhibitory neurotransmitter misbalance, and the participation of brain GABAergic system being very important in particular (Faingold et al, 1994) [7,[23][24][25][26] . This could determine the increased vulnerability to corazol seizures of KM rats as highly AE prone animals.…”

mentioning

confidence: 99%

Subthreshold Corazol Doses Induced Generalized Seizures in Audigenic Seizure-Prone Rats

Полетаева¹

2016

IJNBD

View full text Add to dashboard Cite

Purpose: It was suggested that high audiogenic epilepsy (AE) susceptibility in rats of Krushinsky-Molodkina (KM) rat strain could be accompanied by increase in general seizure proneness. This could be tested exploring the reaction to low corazol doses in these rats and in rats of genetically related but non-prone to AE strain (strain "0"), which was used as control,. Method: 6 months old male rats of two strains (KM and "0") received the subthreshold (40 mg/kg) corazol injections. After injections rats were placed in individual cages and were observed for 40-50 min in order to discover the display/absence of corazol induced convulsions. Results: The typical corazol seizures developed in more than 50% of KM rats (AE-susceptible) in comparison to non-prone control rats, in which these seizures were more rare events. The control rats of "0" strain demonstrated seizures of significantly lower intensity, than in KM rats. Although most rats of "0", which did not express corazol seizures and no AE seizures three weeks before the experiment as well, demonstrated they demonstrated the intense AE seizures when tested 20 min after corazol injection. Conclusions: Rats of KM strain, selected for intense AE seizures, developed generalized seizures in response to subthreshold corazol dose, demonstrating the elevated general seizure proneness

show abstract

Molecular and neurochemical substrates of the audiogenic seizure strains: The GASH:Sal model

Cited by 28 publications

References 52 publications

Analysis of gene variants in the GASH/Sal model of epilepsy

Analysis of gene variants in the GASH/Sal model of epilepsy

From nephron to neuron: an exciting journey in search of a cure for epilepsy

Subthreshold Corazol Doses Induced Generalized Seizures in Audigenic Seizure-Prone Rats

Contact Info

Product

Resources

About