The Role Of The Long Non-coding RNA AK035610 In Epileptogenesis

Objective:In order to establish an animal model of human temporal lobe epilepsy,C57BL/6 mice were induced into epilepticus seizures by kainic acid.To explore the dynamic changes of regulatory networks and functional pathways of lncRNA in the pathogenesis of epilepsy,and provide new evidence for the diagnosis of epilepsy and new targets for anti-epileptic drug development.Methods:C57BL/6 male mice(6-8 weeks)were used as the main tools.The epilepticus seizures mice model was established by intraperitoneal injection of kainic acid.The long non-coding RNA gene microarray was used to detect the abnormalities in the hippocampus of seizures.The expression of lincRNA-AK035610 was comfirmed by real-time quantitative PCR.And the nearby gene Inhba of lincRNA-AK035610 was predicted by bioinformatics to verify.The expression of lincRNA-AK035610 and INHBA was verified by real-time quantitative PCR and immunoblotting in the temporal lobe brain tissue of TLE patients.INHBA recombinant protein is injected into the lateral ventricles of mice induced by KA mouse behavior and EEG changes were observed.Results:1.kainic acid can induce epilepticus seizures in mice,and the corresponding abnormal EEG can be detected simultaneously.LincRNA-AK035610 and lincRNA-AK015830 had abnormal expression in the epilepticus seizures mice model,and we selected lincRNA-AK035610 as the main research object for the following study;2.The expression of lincRNA-AK035610 and Inhba in hippocampus of KA-induced mouse model were significantly up-regulated,and increase in cortical tissues,but no significant statistical difference was observed.The Inhba gene is significantly increased in the hippocampus and cortex tissues of modle mice.The expression of splicing variant 1 and INHBA was similar to the mouse model of epilepsy,but there was no significant correlation between INHBA splicing variant 13'UTR and INHBA in the control group Epilepsy patients have a good correlation in the brain tissue;3.The subcellular localization of lincRNA-AK035610 in neuronal cells is located in the nucleus;4.Recombinant INHBA protein can reduce KA-induced apoptosis;5.Supplement of INHBA alleviates KA-induced seizure to reduce the abnormal EEG level change and prolong the latency time of seizures induced by KA.Conclusion:lincRNA-AK035610(splicing variant 1)and INHBA were significantly increased in the mouse model of seizure and temporal lobe epilepsy patients.And only in the TLE patients brain specimens have significant correlation.It can be used as a biomarker of epilepsy diagnosis,and try to design target drugs for epilepsy treatment.