Top Common Differentially Expressed Genes in the Epileptogenic Nucleus of Two Strains of Rodents Susceptible to Audiogenic Seizures: WAR and GASH/Sal

Abstract

Damasceno et al. Transcriptome GASH/Sal and WAR Models already established in the strains. Our findings suggest that these genes may be causing small changes in different biological processes involved in seizure occurrence and response, and indirectly contributing to the susceptibility of the WAR and GASH/Sal models to audiogenic seizures.

Distribution of the Cannabinoid Receptor Type 1 in the Brain of the Genetically Audiogenic Seizure-Prone Hamster GASH/Sal

“…All tissues harvested were put into storage at −80°C until use. The RT-qPCR approach was identical to that used previously by our group (e.g., Damasceno et al, 2020 ; Sánchez-Benito et al, 2020 ). RNA from samples was extracted in accordance with the protocol of TRIzol ™ Reagent (#15596026, Invitrogen).…”

Behavioral and Molecular Effects Induced by Cannabidiol and Valproate Administration in the GASH/Sal Model of Acute Audiogenic Seizures

“…Each sample tissue was frozen immediately in liquid nitrogen. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) experiments were carried out following the protocol routinely used in our laboratory (López-López et al, 2017;Damasceno et al, 2020;Díaz-Rodríguez et al, 2020;Sánchez-Benito et al, 2020), which is in accordance with published guidelines (Nolan et al, 2006). Briefly, total RNA (2 µg) was mixed with oligo-dT and random hexamer primers for reverse transcription into cDNA using the First Strand cDNA Synthesis Kit (K1621, Promega Corporation, Madison, WI, USA).…”

“…In fact, the innate AGS susceptibility of the GASH/Sal model lies in an upward spread of abnormal glutamatergic transmission throughout the primary acoustic pathway to the inferior colliculus, a critical integration center in the auditory midbrain that is considered the epileptogenic region (Sánchez-Benito et al, 2020). Furthermore, recent studies have found disrupted gene expression profiles in the inferior colliculus of the GASH/Sal under free-seizure conditions and after sound-induced seizures that are associated with seizure susceptibility and altered regulation of neuronal excitability (López-López et al, 2017;Damasceno et al, 2020;Díaz-Casado et al, 2020;Díaz-Rodríguez et al, 2020). In view of this, it becomes of interest to compare patterns of gene expression after each of the treatments in the inferior colliculus of the GASH/Sal, particularly when CBD is coadministered with VPA.…”

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“…These gene expression peculiarities were associated with distinct pathological traits in brain function. On the other hand, other studies showed no changes in the brains of KM rats, concerning the expression of other genes characteristic of WAR and/or GASH/Sal models (Npy, Egr3, and Rgs2) while authors (Damasceno et al, 2020) associated these genes with a predisposition to AE in these animals. Additionally, in KM rats (as in rats of other AE-prone strains), no changes in the expression level of the Vlgr1 gene were reported, while mutation of this gene caused the development of AE in Frings mice (Klein et al, 2005).…”

“…Importantly, high levels of Ttr expression and transthyretin protein and mutations in the Ttr gene were demonstrated in GASH/Sal hamsters and in WAR rats. To this end deficiency of GABAA receptor-mediated neurotransmission were previously shown in GASH/Sal hamster and WAR rat models (Damasceno et al, 2020;Díaz-Casado et al, 2020).…”