Upregulation of salt-inducible kinase 2 promotes seizure susceptibility in epilepsy.

Abstract

Salt-inducible kinase 2 (SIK2) is a serine/threonine kinase implicated in several neurological disorders; however, its role in epilepsy remains unclear. In this study, temporal lobe cortex tissues from patients with temporal lobe epilepsy and control subjects, as well as tissues from epilepsy model mice, were analyzed to investigate the expression and function of SIK2. Western blotting and immunofluorescence were used to measure SIK2 expression and cellular localization in epilepsy model mice. To assess its functional relevance, the overexpression or knockdown of SIK2 in the hippocampus was combined with a chronic PTZ kindling model to evaluate seizure susceptibility and mortality. We found that SIK2 expression was significantly increased in the cortical and hippocampal regions of epileptic mice, as well as in temporal lobe cortex of epilepsy patients, with predominant localization in neurons. Hippocampal overexpression of SIK2 decreased seizure latency, increased seizure severity, and increased mortality, whereas SIK2 knockdown had the opposite effects. These findings indicate that SIK2 contributes to seizure susceptibility and epileptogenesis and may represent a potential molecular target for epilepsy intervention.