Increased Expression of MST1 in Patients With Epilepsy and in a Rat Model of Epilepsy.

Abstract

Mammalian sterile20-like kinase 1 (MST1), a serine/threonine kinase frequently expressed, has emerged as pivotal modulator of multiple physiological and pathological conditions such as cellular growth, programmed cell death, oxidative stress, neurodegeneration, inflammation, and synaptic plasticity in the central nervous system. Various neurological diseases are associated with the activation of MST1. Epilepsy is a severe neurological disorder characterized by abrupt abnormal electrical activity in the brain and recurring spontaneous seizures. The most common pathological discoveries in patients and animal models with epilepsy are neuronal death, inflammation, neurodegeneration, neurogenesis, and axonal regrowth. The purpose of this study was to assess the levels of MST1 in serum and cerebrospinal fluid (CSF) specimens obtained from individuals diagnosed with epilepsy. In addition, it aimed to explore the expression pattern of MST1 in brain tissues of epileptic rats. We used enzyme-linked immunosorbent assay to measure the levels of CSF and serum MST1 in 10 epilepsy patients and 9 control patients. After creation of epilepsy models with healthy male Sprague-Dawley rats using lithium and pilocarpine, the expression of MST1 in the temporal cortex and hippocampus was evaluated at different time points (6 h, 24 h, 3 days, 7 days, 14 days, and 30 days after seizures) using immunofluorescence, immunohistochemistry, and Western blotting. In patients with epilepsy, the levels of CSF-MST1 were elevated (593.90 ± 16.28 vs. 560.40 ± 19.42 pg/mL, p < 0.05) compared to the control group. Accordingly, the serum-MST1 levels were 583.40 ± 19.70 pg/mL in the epilepsy group and 555.70 ± 20.14 pg/mL in the control group, demonstrating a statistically significant distinction (p < 0.05). Levels of MST1 in CSF and serum could be of diagnostic help. Neuronal apoptosis in temporal cortex and hippocampus of epileptic rats was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. MST1 was expressed in the neuronal membrane and cytoplasm of the temporal cortex and hippocampus. The expression of MST1 increased after seizures, showing a relatively high level within 30 days and reaching its highest point on the seventh day after status epilepticus. The findings of this study indicate that the increased expression of MST1 protein in patients with epilepsy and epileptic rats might play a role in the development of epilepsy.