A Study On The Expression Of TNIK In Brain Tissue Of Patients With Temporal Lobe Epilepsy And Epileptic Animal Models

BackgroundEpilepsy is a common neurological syndrome caused by abnormal nervous discharge of neurons,which occurs at all ages.Nowadays,it has become a global health problem,which brings a heavy burden to tens of millions of families.Up to now,drug therapy is the main approach of clinical epilepsy treatment,but after systemic and standardized drug treatment,about 30%of patients still have difficulty in effective control of seizures,which is called refractory epilepsy.Data shows that epilepsy is closely related to abnormalities in neurotransmitters,ion channels,glial cells and oxidative stress.However,the causes of refractory epilepsy are even more complicated.Finding new specific targets for epilepsy and studying their mechanisms are always the focus of relevant researchers.As a multifunctional protein of the germinal center kinase family,TNIK can mediate various physiological functions such as apoptosis and excitatory signal transduction by regulating different signaling pathways.Therefore,clarifying potential roles and exploring possible mechanisms of TNIK in epilepsy are of great practical significance.ObjectiveTo explore the relationship between TNIK and epilepsy by investigating the expression of TNIK in patients with temporal lobe epilepsy and pilocarpine-induced chronic epileptic animal models.Methods20 samples were randomly collected as epilepsy group from the brain tissue bank of patients undergoing refractory temporal lobe epilepsy surgery.10 patients who treated with decompression of craniocerebral trauma were selected at random and their brain tissue samples were used as control group.Healthy adult male Sprague Dawley rats weighing 210-230g were randomly selected and given intraperitoneal injection of pilocarpine to induce status epilepticus.Two month later,animal models of chronic epilepsy were finally established.Rats were included in the control group after intraperitoneal injection of the same amount of saline under the same conditions.The localization of TNIK in brain tissue was investigated by immunofluorescence staining.The expression levels of TNIK in brain tissue of patients with temporal lobe epilepsy and chronic epileptic rats were examined by Western blotting,qPCR and immunohistochemistry.ResultsIn brain tissue of temporal lobe epilepsy patients and pilocarpine-induced chronic epileptic rats,TNIK colocalizes with the neuronal marker MAP2.It mainly localized in neurons,but not in astrocytes.The expression level of TNIK protein in brain tissue of patients with refractory temporal lobe epilepsy was significantly lower than that of the control group(p<0.01).In pilocarpine-induced chronic epileptic animal models,the expression level of TNIK protein in hippocampus and cortex of rats was significantly lower than that of the control group(p<0.01);The relative expression level of TNIK gene in hippocampus of the epilepsy group was significantly lower than that of the control group(p<0.01).The relative expression level of TNIK gene in the cortex of the epilepsy group was lower than that of the control group(p<0.05).ConclusionThe expression level of TNIK in the brain tissue of patients with temporal lobe epilepsy and pilocarpine-induced chronic epileptic rats were decreased.Moreover,TNIK was mainly expressed in neurons,indicating that TNIK is likely to play an essential role in the development of epilepsy.