Behavioral and neurochemical characterization of the spontaneous mutation tremor, a new mouse model of audiogenic seizures.

Autor: Garcia-Gomes MSA; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Brazil. Electronic address: mari-aranha@usp.br., Zanatto DA; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Brazil., Galvis-Alonso OY; Department of Molecular Biology, Medicine School of São José do Rio Preto (FAMERP), Brazil., Mejia J; Hospital Israelita Albert Einstein, São Paulo, Brazil., Antiorio ATFB; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Brazil., Yamamoto PK; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Brazil., Olivato MCM; Federal University of São Paulo (UNIFESP), Brazil., Sandini TM; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Brazil., Flório JC; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Brazil., Lebrun I; Laboratory of Biochemistry and Biophysics, Butantan Institute, Brazil., Massironi SMG; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP), Brazil., Alexandre-Ribeiro SR; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP), Brazil., Bernardi MM; Paulista University, Brazil., Ienne S; Core Facility for Scientific Research - University of São Paulo (CEFAP-USP/GENIAL (Genome Investigation and Analysis Laboratory), Brazil., de Souza TA; Department of Microbiology, Institute of Biomedical Science, University of São Paulo (USP), Brazil., Dagli MLZ; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Brazil., Mori CMC; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Epilepsy & behavior : E&B [Epilepsy Behav] 2020 Apr; Vol. 105, pp. 106945. Date of Electronic Publication: 2020 Feb 25.
DOI: 10.1016/j.yebeh.2020.106945
Abstrakt: The tremor mutant phenotype results from an autosomal recessive spontaneous mutation arisen in a Swiss-Webster mouse colony. The mutant mice displayed normal development until three weeks of age when they began to present motor impairment comprised by whole body tremor, ataxia, and decreased exploratory behavior. These features increased in severity with aging suggesting a neurodegenerative profile. In parallel, they showed audiogenic generalized clonic seizures. Results from genetic mapping identified the mutation tremor on chromosome 14, in an interval of 5 cM between D14Mit37 (33.21 cM) and D14Mit115 (38.21 cM), making Early Growth Response 3 (Egr3) the main candidate gene. Comparing with wild type (WT) mice, the tremor mice showed higher hippocampal gene expression of Egr3 and Gabra1 and increased concentrations of noradrenalin (NOR; p = .0012), serotonin (5HT; p = .0083), 5-hydroxyindoleacetic acid (5-HIAA; p = .0032), γ-amino butyric acid (GABA; p = .0123), glutamate (p = .0217) and aspartate (p = .0124). In opposition, the content of glycine (p = .0168) and the vanillylmandelic acid (VMA)/NOR ratio (p = .032) were decreased. Regarding to dopaminergic system, neither dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents nor the turnover rate of DA showed statistically significant differences between WT and mutant mice. Data demonstrated that audiogenic seizures of tremor mice are associated with progressive motor impairment as well as to hippocampal alterations of the Egr3 and Gabra1 gene expression and amino acid and monoamine content. In addition, the tremor mice could be useful for study of neurotransmission pathways as modulators of epilepsy and the pathogenesis of epilepsies occurring with generalized clonic seizures.
Competing Interests: Declaration of competing interest We have no conflicts of interest to declare. All authors declare no competing interests.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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