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

Author(s):Show less -

Aranha Garcia-Gomes, Mariana de Souza ^[1] ; Zanatto, Dennis Albert ^[1] ; Galvis-Alonso, Orfa Yineth ^[2] ; Mejia, Jorge ^[3] ; Fonseca Brasil Antiorio, Ana Tada ^[1] ; Yamamoto, Pedro Kenzo ^[1] ; Millan Olivato, Marcia Carolina ^[4] ; Sandini, Thaisa Meira ^[1] ; Florio, Jorge Camilo ^[1] ; Lebrun, Ivo ^[5] ; Gomes Massironi, Silvia Maria ^{[6, 1]} ; Alexandre-Ribeiro, Sandra Regina ^[6] ; Bernardi, Maria Martha ^[7] ; Ienne, Susan ^[8] ; de Souza, Tiago Antonio ^[9] ; Zaidan Dagli, Maria Lucia ^[1] ; Cabrera Mori, Claudia Madalena ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, Av Prof Dr Orlando Marques de Paiva 87, BR-05508270 Sao Paulo - Brazil

^[2] Med Sch Sao Jose do Rio Preto FAMERP, Dept Mol Biol, Sao Jose Do Rio Preto - Brazil

^[3] Hosp Israelita Albert Einstein, Sao Paulo - Brazil

^[4] Fed Univ Sao Paulo UNIFESP, Sao Paulo - Brazil

^[5] Butantan Inst, Lab Biochem & Biophys, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[7] Univ Paulista, Sao Paulo - Brazil

^[8] Univ Sao Paulo, Core Facil Sci Res, CEFAP USP GENIAL Genome Invest & Anal Lab, Sao Paulo - Brazil

^[9] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Epilepsy & Behavior; v. 105, APR 2020.
• Web of Science Citations: 0

Abstract

The tremor mutant phenotype results from an autosomal recessive spontaneous mutation arisen in a SwissWebster 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 donic 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 Gabral and increased concentrations of noradrenalin (NOR; p = .0012), serotonin (BHT; p = .0083), 5-hydroxyindoleacetic acid (5-HIM; p = .0032). gamma-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 Cabral gene expression and amino add 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. (C) 2020 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 17/21103-3 - Phenotypic and molecular characterization of two mutant mice strains with motor and sensorial impairment as potential models for the study of neurological diseases
• Grantee: Claudia Madalena Cabrera Mori
• Support Opportunities: Regular Research Grants