title: Neuroligin-1 Knockdown Suppresses Seizure Activity by Regulating Neuronal Hyperexcitability.
abstract: Abnormally synchronized synaptic transmission in the brain leads to epilepsy. Neuroligin-1 (NL1) is a synaptic cell adhesion molecule localized at excitatory synapses. NL1 modulates synaptic transmission and determines the properties of neuronal networks in the mammalian central nervous system. We showed that the expression of NL1 and its binding partner neurexin-1β was increased in temporal lobe epileptic foci in patients and lithium-pilocarpine-treated epileptic rats. We investigated electrophysiological and behavioral changes in epileptic rats after lentivirally mediated NL1 knockdown in the hippocampus to determine whether NL1 suppression prevented seizures and, if so, to explore the probable underlying mechanisms. Our behavioral studies revealed that NL1 knockdown in epileptic rats reduced seizure severity and increased seizure latency. Whole-cell patch-clamp recordings of CA1 pyramidal neurons in hippocampal slices from NL1 knockdown epileptic rats revealed a decrease in spontaneous action potential frequency and a decrease in miniature excitatory postsynaptic current (mEPSC) frequency but not amplitude. The amplitude of N-methyl-D-aspartate receptor (NMDAR)-dependent EPSCs was also selectively decreased. Notably, NL1 knockdown reduced total NMDAR1 expression and the surface/total ratio in the hippocampus of epileptic rats. Taken together, these data indicate that NL1 knockdown in epileptic rats may reduce the frequency and severity of seizures and suppress neuronal hyperexcitability via changes in postsynaptic NMDARs.
authors.affiliation: Department of Emergency and Intensive Care Unit, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors.forename: Jin-Lai
authors.initials: JL
authors.lastname: Wei
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors.forename: Zhao-Hua
authors.initials: ZH
authors.lastname: Tang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China. wangxfyp@163.com.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002648:Child; D004195:Disease Models, Animal; D015536:Down-Regulation; D004827:Epilepsy; D005260:Female; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012640:Seizures / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D013569:Synapses / Q000378:metabolism; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D019006:Neural Cell Adhesion Molecules; D016194:Receptors, N-Methyl-D-Aspartate; C093438:neuroligin 1
keywords: Cortex; Hippocampus; NMDAR; Neuroligin-1; Temporal lobe epilepsy