Alteration of hippocampal Egr3, GABA A receptors, Il-10, Il6 and Ccl3 expression in audiogenic tremor mice after seizure

Author(s)

Garcia-Gomes, Mariana de Souza Aranha ; Yamamoto, Pedro Kenzo ; Massironi, Silvia Maria Gomes ; Galvis-Alonso, Orfa Yineth ; Mejia, Jorge ; Zanatto, Dennis Albert ; Alexandre-Ribeiro, Sandra Regina ; Ienne, Susan ; Mori, Claudia Madalena Cabrera

• Document type: Journal article
• Source: Epilepsy & Behavior; v. 137, p. 5-pg., 2022-11-07.

Abstract

Neuroinflammation plays a protective role in the brain; however, in neurological diseases such as epi-lepsy, overactivated neuroinflammation, along with overexpression of inflammatory mediators, can cause neuronal tissue damage, which can trigger seizures due to loss of ionic or neurotransmitter home-ostasis. Therefore, we aimed to evaluate mRNA expression levels of proinflammatory cytokines, early growth response factor 3 (Egr3), and GABA A receptors in the hippocampus of naive audiogenic mutant tremor mice, and stimulated tremor mice after a seizure. Gene expression of Il-10, Il-6, Tnf-a, Ccl2, Ccl3, Egr3, Gabra1, and Gabra4 from hippocampal samples of naive and stimulated tremor mice were mea-sured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Relative to resistant mice, Ccl3 gene expression was increased and Il6 was decreased in the hippocampus of naive tremor mice. Thirty minutes after a seizure, Ccl3 and Il-10 mRNA expression were decreased (p < 0.0001; p = 0.0034, respectively) while Il6 was increased (p = 0.0052) in stimulated tremor mice, relative to naive animals. In addition, Egr3, Gabra1, and Gabra4 mRNA expression was decreased in the hippocampus of naive tremor mice, relative to resistant mice, which increased 30 minutes after a seizure (p = 0.0496; p = 0.0447, and p = 0.0011, respectively), relative to naive animals. In conclusion, overexpression of Ccl3 in the hippocampus of naive tremor mice, followed by downregulation soon after seizure in stimu-lated tremor mice, could be involved in changes in the blood-brain barrier (BBB) permeability in epilepsy. Il-10 may be involved in hippocampal downregulation of GABA A receptors of naive tremor mice, char-acterizing an important mechanism in audiogenic seizures triggering. Hippocampal alterations of proin-flammatory cytokines, Egr3, and GABA A receptors in tremor mice reinforce them as an alternative tool to modeling temporal lobe epilepsy.(c) 2022 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