title: Overexpression of the immediate-early genes Egr1, Egr2, and Egr3 in two strains of rodents susceptible to audiogenic seizures.
abstract: Genetic animal models of epilepsy are an important tool for further understanding the basic cellular mechanisms underlying epileptogenesis and for developing novel antiepileptic drugs. We conducted a comparative study of gene expression in the inferior colliculus, a nucleus that triggers audiogenic seizures, using two animal models, the Wistar audiogenic rat (WAR) and the genetic audiogenic seizure hamster (GASH:Sal). For this purpose, both models were exposed to high intensity auditory stimulation, and 60min later, the inferior colliculi were collected. As controls, intact Wistar rats and Syrian hamsters were subjected to stimulation and tissue preparation protocols identical to those performed on the experimental animals. Ribonucleic acid was isolated, and microarray analysis comparing the stimulated Wistar and WAR rats showed that the genomic profile of these animals displayed significant (fold change, |FC|≥2.0 and p<0.05) upregulation of 38 genes and downregulation of 47 genes. Comparison of gene expression profiles between stimulated control hamsters and stimulated GASH:Sal revealed the upregulation of 10 genes and the downregulation of 5 genes. Among the common genes that were altered in both models, we identified the zinc finger immediate-early growth response gene Egr3. The Egr3 protein is a transcription factor that is induced by distinct stress-elicited factors. Based on immunohistochemistry, this protein was expressed in the cochlear nucleus complex, the inferior colliculus, and the hippocampus of both animal models as well as in lymphoma tumors of the GASH:Sal. Our results support that the overexpression of the Egr3 gene in both models might contribute to neuronal viability and development of lymphoma in response to stress associated with audiogenic seizures. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
authors.affiliation: Institute for Neuroscience of Castilla y León (INCyL), University of Salamanca, Salamanca, Spain; Salamanca Institute for Biomedical Research (IBSAL), Spain.
authors.forename: D
authors.initials: D
authors.lastname: López-López
authors.affiliation: Institute for Neuroscience of Castilla y León (INCyL), University of Salamanca, Salamanca, Spain; Salamanca Institute for Biomedical Research (IBSAL), Spain; Department of Cell Biology and Pathology, School of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Gómez-Nieto
authors.affiliation: Institute for Neuroscience of Castilla y León (INCyL), University of Salamanca, Salamanca, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Herrero-Turrión
authors.affiliation: Physiology Department, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: N
authors.initials: N
authors.lastname: García-Cairasco
authors.affiliation: Institute for Neuroscience of Castilla y León (INCyL), University of Salamanca, Salamanca, Spain; Salamanca Institute for Biomedical Research (IBSAL), Spain.
authors.forename: D
authors.initials: D
authors.lastname: Sánchez-Benito
authors.affiliation: Department of Cell Biology and Pathology, School of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Ludeña
authors.affiliation: Institute for Neuroscience of Castilla y León (INCyL), University of Salamanca, Salamanca, Spain; Salamanca Institute for Biomedical Research (IBSAL), Spain; Department of Cell Biology and Pathology, School of Medicine, University of Salamanca, Salamanca, Spain. Electronic address: lopezde@usal.es.
authors.forename: D E
authors.initials: DE
authors.lastname: López
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects*; D000818:Animals; D006224:Cricetinae; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000235:genetics*; D051767:Early Growth Response Protein 2 / Q000096:biosynthesis / Q000235:genetics*; D051776:Early Growth Response Protein 3 / Q000096:biosynthesis / Q000235:genetics*; D020195:Epilepsy, Reflex / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D017781:Genes, Immediate-Early / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D051381:Rats; D017208:Rats, Wistar; D012377:Rodentia; D012640:Seizures / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity
chemical_list: D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; C486110:Egr1 protein, rat; C497328:Egr2 protein, rat; C497370:Egr3 protein, rat; D051776:Early Growth Response Protein 3
keywords: Audiogenic epilepsy; Early growth response; GASH:Sal; Microarray; Seizure-induced transcriptome; WAR