Subicular pyramidal neurons gate drug resistance in temporal lobe epilepsy  

作　　者：XU Ceng-lin WANG Yi CHEN Zhong 

机构地区：[1]Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, College of Pharmaceutical Sciences, School of Medicine, Zhejiang University, Hangzhou 310058, China

出　　处：《中国药理学与毒理学杂志》2018年第9期722-723,共2页Chinese Journal of Pharmacology and Toxicology

基　　金：National Natural Science Foundation of China(91332202,81630098,81521062,81671282,81703480).

摘　　要：OBJECTIVE To understand the underlying mechanisms of drug resistant temporal lobe epilepsy(TLE).METHODS In vivo and vitro electrophysiology,optogenetics and chemogenetics were used in a classic multi-drug resistant TLE model.RESULTS Subicular pyramidal neuron activity was not inhibited by the anti-epileptic drug phenytoin in drug resistant rats.This phenomenon was specific to the subiculum,but did not involve surrounding temporal lobe regions.Selective inhibition of subicular pyramidal neurons by both optogenetics and chemogenetics reversed drug resistance.In contrast,selective activation of subicular pyramidal neurons directly induced drug resistance in drug responsive rats.Furthermore,long-term low frequency stimulation at the subiculum,which is clinically feasible,inhibited the activity of subicular pyramidal neurons and reversed drug resistance.CONCLUSION Subicular pyramidal neurons might be a key ″ switch″ mediating drug resistance in TLE and represent a new potential target for more precise treatment of drug resistant TLE.OBJECTIVE To understand the underlying mechanisms of drug resistant temporal lobe epilepsy(TLE).METHODS In vivo and vitro electrophysiology,optogenetics and chemogenetics were used in a classic multi-drug resistant TLE model.RESULTS Subicular pyramidal neuron activity was not inhibited by the anti-epileptic drug phenytoin in drug resistant rats.This phenomenon was specific to the subiculum,but did not involve surrounding temporal lobe regions.Selective inhibition of subicular pyramidal neurons by both optogenetics and chemogenetics reversed drug resistance.In contrast,selective activation of subicular pyramidal neurons directly induced drug resistance in drug responsive rats.Furthermore,long-term low frequency stimulation at the subiculum,which is clinically feasible,inhibited the activity of subicular pyramidal neurons and reversed drug resistance.CONCLUSION Subicular pyramidal neurons might be a key ″ switch″ mediating drug resistance in TLE and represent a new potential target for more precise treatment of drug resistant TLE.

关 键 词：temporal LOBE EPILEPSY SUBICULUM PYRAMIDAL NEURONS 

分 类 号：R[医药卫生]