Subunit specific altered expression and activity of casein kinase 2 in the brain tissues resected from mesial temporal lobe epilepsy with hippocampal sclerosis patients & rodent temporal lobe epilepsy model

Abstract

Introduction

Mesial temporal lobe epilepsy (MTLE), is associated with dysregulated excitatory-inhibitory balance in the brain. Numerous enzymes, protein kinases, that are modulated through phosphorylation, have been linked with key processes involved in the pathogenesis of epilepsy. Therefore, in this study, we determined the subunit specific expression and activity of multi-subunit casein Kinase 2 (CK2) which influences NMDARs through phosphorylation events, in MTS patients as well as pilocarpine model of TLE.

Methods

mRNA expression of CK2 (α, α’, β) & NR2B was measured by real time PCR and protein expression of CK2 (α, α’, β), NR2B, and NR2B Ser1480 were evaluated using western blotting and immunohistochemistry in experimental models of TLE and MTS patients. CK2 α and α’ activity was measured by kinase assay.

Results

Significant increase in CK2α’, CK2β, and NR2B mRNA expression were noted in chronic TLE rat model. Similarly, MTS patients displayed upregulated CK2α’ and CK2β expressions, but NR2B mRNA remained unchanged. CK2α’, CK2β, and NR2B Ser1480 protein expressions were higher in chronic TLE and MTS patients in relation to controls (p < 0.05), as was kinase activity (p < 0.05). In acute TLE rats, only NR2B protein expression was upregulated (p < 0.05).

Conclusion

Our research demonstrated for the first time the upregulation of CK2α’ subunit and its increased kinase activity in resected brain samples from MTS patients as well as pilocarpine model of TLE. Altered expression and higher activity of CK2 α’ highlights subunit specific contribution, suggesting the modulation of NMDA receptors by Casein Kinase 2 may contribute to hyperexcitability in MTLE.