Pharmacological and neuroethological studies of three antiepileptic drugs in the Genetic Audiogenic Seizure Hamster (GASH:Sal)

Barrera-Bailón, Biviana; Oliveira, José Antônio Cortes de; López, Dolores E.; Muñoz, Luis J.; García-Cairasco, Norberto; Sancho, Consuelo

doi:10.1016/j.yebeh.2013.05.028

Cited by 23 publications

(43 citation statements)

References 59 publications

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“…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

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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.

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Section: Plos Onementioning

confidence: 99%

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

et al. 2020

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“…The control and GASH/Sal animals that were exposed to loud sound stimulation were individually placed within an acrylic cylinder to receive a single high-intensity acoustic stimulus for 10 s. The stimulus used in the high-intensity acoustic stimulation protocol was recorded using a high-pass filter (N500 Hz; microphone Bruel and Kjaer #4134 and preamplifier Bruel and Kjaer #2619), digitized above 4 kHz, and reproduced by a computer coupled to an amplifier (Fonestar MA-25T, Revilla de Camargo, Spain) and a tweeter (Beyma T2010, Valencia, Spain) in the upper portion of the arena. The delivered sound was a semirandom acoustic stimulus of 0-18 kHz with an intensity of 115 to 120 dB (Barrera-Bailón et al, 2013;López-López et al, 2017).…”

Section: Methodology Animalsmentioning

confidence: 99%

“…These animals reach their maximum degree of seizure susceptibility between the second and fourth month of life, which then gradually disappears (Muñoz et al, 2017), and their seizures have been characterized as complete sound-evoked reflex seizures (Carballosa-Gonzalez et al, 2013). Furthermore, several studies have reported the inheritance pattern (Muñoz et al, 2017), and the neuroanatomical substrates underlying audiogenic seizure susceptibility (Sánchez-Benito et al, 2017 as well as the anticonvulsant effects after antiepileptic drug administration (Barrera-Bailón et al, 2013. It has also been found that the GASH/Sal exhibits altered gene expression of early growth response genes 1 to 3 (Egr1, Egr2, and Egr3) in the IC, presumably as an effect of stress associated to seizures (López-López et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Inferior Colliculus Transcriptome After Status Epilepticus in the Genetically Audiogenic Seizure-Prone Hamster GASH/Sal

et al. 2020

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“…Finally, in addition to being able to reliably reproduce the objective symptoms and EEG features of the epilepsy syndrome, it is also able to respond to different antiepileptic drugs (AEDs), such as phenobarbital, valproic acid, and levetiracetam [112], so the GASH:Sal is a reliable animal model of epilepsy.…”

Section: Relevance Of the Modelmentioning

confidence: 99%

The genetic audiogenic seizure hamster from Salamanca: The GASH:Sal

Muñoz

Carballosa-Gautam

Yanowsky

et al. 2017

Epilepsy & Behavior

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The hamster has been previously described as a paroxysmal dystonia model, but our strain is currently recognized as a model of audiogenic seizures (AGS). The original first epileptic hamster appeared spontaneously at the University of Valladolid, where it was known as the GPG:Vall line, and was transferred to the University of Salamanca where a new strain was developed, named GASH:Sal. By testing auditory brainstem responses, the GASH:Sal exhibits elevated auditory thresholds that indicate a hearing impairment. Moreover, amplified fragment length polymorphism analysis distinguished genetic differences between the susceptible GASH:Sal hamster strain and the control Syrian hamsters. The GASH:Sal constitutes an experimental model of reflex epilepsy of audiogenic origin derived from an autosomal recessive disorder. Thus, the GASH:Sal exhibits generalized tonic-clonic seizures, characterized by a short latency period after auditory stimulation, followed by wild running, a convulsive phase, and finally stupor, with origin in the brainstem. The seizure profile of the GASH:Sal is similar to those exhibited by other models of inherited AGS susceptibility, which decreases after six months of age, but the proneness across generations is maintained. The GASH:Sal can be considered a reliable model of audiogenic seizures, suitable to investigate current antiepileptic pharmaceutical treatments as well as novel therapeutic drugs.This article is part of a Special Issue entitled Genetic Models-Epilepsy.

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Pharmacological and neuroethological studies of three antiepileptic drugs in the Genetic Audiogenic Seizure Hamster (GASH:Sal)

Cited by 23 publications

References 59 publications

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

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

Inferior Colliculus Transcriptome After Status Epilepticus in the Genetically Audiogenic Seizure-Prone Hamster GASH/Sal

The genetic audiogenic seizure hamster from Salamanca: The GASH:Sal

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