The role of glutamine synthetase expression and cystine/glutamate transporter (SLC7A11, xCT) in epilepsy pathogenesis of patients with supratentorial brain gliomas

Abstract

Background. Epileptic seizures represent one of the leading clinical manifestations of glial brain tumors that develop on average in 51% of cases. In gliomas, epileptogenesis is quite complex and multifactorial.Objective: to study a role of the expressed glutamine synthetase enzyme, as well as cystine/glutamate transporter (xCT system, SLC7A11) in the pathogenesis of epilepsy developing in patients with cerebral gliomas.Material and methods. The study included 32 patients with supratentorial gliomas. The average age of the disease onset (diagnosis) was 50.69±18.01 years. All patients underwent inpatient examination and treatment at the Neurosurgery and Nervous Diseases Clinics of Kirov Military Medical Academy from 2018 to 2020. In all cases, a biopsy of tumor tissue was collected. Histological and immunohistochemical studies were performed (expression of glutamine synthetase and cystine/ glutamate transporter (SLC7A11, xCT)).Results. Significant (ANOVA p=0.027, Mann–Whitney U-test p=0.033) differences in the expression of cystine/glutamate transporter (xCT system, SLC7A11) were revealed, by showing the following median values (lower quartile; upper quartile): 50% (45; 75) in the group of patients with seizures, 40% (40; 50) in the seizure-free group. The expression level of glutamine synthetase did not significantly differ in the groups with and without seizures.Conclusion. The data obtained confirmed that one of the pathogenetic mechanisms for epilepsy development in patients with gliomas was related to highly expressed cystine/glutamate transporter (xCT system, SLC7A11) and, as a consequence, an increase in the extracellular glutamate level.

Keywords

• glioma
• epilepsy
• glutamine synthetase
• cystine/glutamate transporter (slc7a11
• xct)
• epilepsy pathogenesis