Apoptotic Markers Are Increased in Epilepsy Patients: A Relation with Manganese Superoxide Dismutase Ala16Val Polymorphism and Seizure Type through IL-1β and IL-6 Pathways.

Aline Kegler,Ana Letícia Fornari Caprara,Patricia Gabbi,Luiz Fernando Freire Royes,Ana Flavia Furian,Eduardo Tanuri Pascotini,Michele Rechia Fighera,Mauro Schneider Oliveira,Marta M M F Duarte,Josi Arend

doi:10.1155/2020/6250429

Aline Kegler, Ana Letícia Fornari Caprara + Show 8 more

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https://doi.org/10.1155/2020/6250429

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Abstract

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has been associated with different diseases. However, there are scarcely studies relating this SNP in epilepsy, a neurologic disease that involves some interacting pathways, such as apoptotic and inflammatory factors. In this sense, we decided to investigate the relationship of MnSOD Ala16Val SNP with apoptotic markers in epilepsy and its relation with inflammatory pathway and seizure type. Ninety subjects were evaluated (47 epilepsies; 43 controls) by questionnaires and laboratorial exams. We observed a higher percentage of VV genotype in the epilepsy group when compared to the control group. IL-1β, IL-6, caspase-1, and caspase-3 levels were increased in the epilepsy group (VV genotype). Furthermore, an important correlation between IL-1β vs. caspase-1 and IL-6 vs. caspase-3 was observed in the epilepsy group (VV genotype). The epilepsy group which presented generalized seizures also demonstrated a positive correlation between IL-1β vs. CASP1 and IL-6 vs. CASP3. Thus, it is a plausible propose that epilepsy patients with VV genotype and generalized seizures present a worse inflammatory and apoptotic status. Our findings suggest that the knowledge of MnSOD Ala16Val polymorphism existence is important to evaluate molecular mechanisms associated to seizure and improve the treatment of these patients.

Highlights

Epilepsy is one of the most common neurological disorders [1] characterized by an enduring predisposition to generate seizures [2] affecting more than 65 million people worldwide [3]
When the brain is affected by brain diseases, the microglia cells are activated [13], and this activation may lead to production of inflammatory cytokines as IL-β [14] and IL-6 [15]
According to Chi-square analysis, no statistically difference was observed between the epilepsy group and control group relating with sex (p = 0:5) and age (p = 0:6)

Summary

Introduction

Epilepsy is one of the most common neurological disorders [1] characterized by an enduring predisposition to generate seizures [2] affecting more than 65 million people worldwide [3]. The excessive activation of microglia may be harmful, promoting the development of neuronal diseases by producing large amounts of inflammatory molecules, such as IL-6 [8], IL-1β, and reactive oxygen species (ROS) [9]. There is a complex cascade of molecular and cell mechanisms involved in excitotoxicity [10], oxidative stress [11], and inflammation [4] beyond cytotoxicity mediated by cytokines [8] and cell death pathway activation [12]. When the brain is affected by brain diseases (i.e., epilepsy), the microglia cells are activated [13], and this activation may lead to production of inflammatory cytokines as IL-β [14] and IL-6 [15]. Manganese superoxide dismutase (MnSOD) antioxidant enzyme is the only known major defense against reactive oxygen species within mitochondria [17]. Montano et al [21] demonstrated that the VV and AV peripheral blood mononuclear cells (PBMC) presented increased levels of inflammatory cytokines as IL-1β and IL-6

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