Epilepsy is one of the most common neurological disorders characterized by epileptic seizures.The anti-epileptic drugs(AEDs)are the main form of treatment for people with epilepsy.Classically,people thought that AEDs ...Epilepsy is one of the most common neurological disorders characterized by epileptic seizures.The anti-epileptic drugs(AEDs)are the main form of treatment for people with epilepsy.Classically,people thought that AEDs modify the activities of ion channels to suppress epileptic seizures.However,accumulating evidence suggests that targeting at ion channels cannot completely account for the numerous effects of the AEDs on its broad clinical activity in epileptic patients.In our study,proteomic methods were used to quantify the proteome of hippocampal tissues from patients who were treated or not treated by AEDs(Carbamazepine).Further bioinformatics methods,including Gene Ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,were utilized to analyze the differences between two patient groups.We found that more than 400 proteins,including metabolism and immune related proteins,had a higher expression level in the carbamazepine-treated group compared with the controls.These altered proteins were considered to be involved in many different biological pathways.Among these pathways,immune-system related pathway modulated by complement C3 and microglia was highly remarkable,which regulated the synapses elimination in physiological condition.In epilepsy,the carbamazepine induced up-regulation of complement C3 might decrease the abnormal synaptic connections between neurons and thus contribute to the therapeutic role of carbamazepine.The results of our study suggested that apart from ion channels,carbamazepine exerted numerous effects on human epileptic foci,which might be the fundamental mechanisms of AEDs for treatment,adverse-effects and pharmacoresistance of epilepsy.展开更多
基金The Ministry of Science and Technology of China(Grant No.2015CB559200)the National Natural Science Foundation of China(Grant No.81371432).
文摘Epilepsy is one of the most common neurological disorders characterized by epileptic seizures.The anti-epileptic drugs(AEDs)are the main form of treatment for people with epilepsy.Classically,people thought that AEDs modify the activities of ion channels to suppress epileptic seizures.However,accumulating evidence suggests that targeting at ion channels cannot completely account for the numerous effects of the AEDs on its broad clinical activity in epileptic patients.In our study,proteomic methods were used to quantify the proteome of hippocampal tissues from patients who were treated or not treated by AEDs(Carbamazepine).Further bioinformatics methods,including Gene Ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,were utilized to analyze the differences between two patient groups.We found that more than 400 proteins,including metabolism and immune related proteins,had a higher expression level in the carbamazepine-treated group compared with the controls.These altered proteins were considered to be involved in many different biological pathways.Among these pathways,immune-system related pathway modulated by complement C3 and microglia was highly remarkable,which regulated the synapses elimination in physiological condition.In epilepsy,the carbamazepine induced up-regulation of complement C3 might decrease the abnormal synaptic connections between neurons and thus contribute to the therapeutic role of carbamazepine.The results of our study suggested that apart from ion channels,carbamazepine exerted numerous effects on human epileptic foci,which might be the fundamental mechanisms of AEDs for treatment,adverse-effects and pharmacoresistance of epilepsy.
