"Clptm1, a new target in suppressing epileptic seizure by regulating GABA(A)R-mediated inhibitory synaptic transmission in a PTZ-induced epilepsy model"

作者全名："Zhang, Xiao-Lin; Zhou, Jin-Yu; Zhang, Peng; Lin, Lan; Mei, Rong; Zhang, Feng-Li; Chen, Yang-Mei; Li, Rong"

作者地址："[Zhang, Xiao-Lin; Lin, Lan; Mei, Rong; Zhang, Feng-Li; Li, Rong] Kunming Univ Sci & Technol, Peoples Hosp Yunnan Prov 1, Affiliated Hosp, Dept Neurol, Kunming, Yunnan, Peoples R China; [Zhou, Jin-Yu] Chongqing Med Univ, Affiliated Hosp 2, Dept Rehabil Med, Chongqing, Peoples R China; [Zhang, Peng; Chen, Yang-Mei] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing, Peoples R China; [Li, Rong] Kunming Univ Sci & Technol, Peoples Hosp Yunnan Prov 1, Affiliated Hosp, Dept Neurol, 157 Jinbi Rd, Kunming 650034, Yunnan, Peoples R China"

通信作者："Li, R (通讯作者)，Kunming Univ Sci & Technol, Peoples Hosp Yunnan Prov 1, Affiliated Hosp, Dept Neurol, 157 Jinbi Rd, Kunming 650034, Yunnan, Peoples R China."

来源：KAOHSIUNG JOURNAL OF MEDICAL SCIENCES

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000899167100001

JCR分区：Q3

影响因子：3.3

年份：2023

卷号：39

期号：1

开始页：61

结束页：69

文献类型：Article

关键词：Clptm1; epileptic seizure; GABA(A)R gamma 2; inhibitory synaptic transmission

摘要："Disruption of gamma-amino butyric acid type A receptors (GABA(A)Rs) synaptic clustering and a decrease in the number of GABA(A)Rs in the plasma membrane are thought to contribute to alteration of the balance between excitatory and inhibitory neurotransmission, which promotes seizure induction and propagation. The multipass transmembrane protein cleft lip and palate transmembrane protein 1 (Clptm1) controls the forward trafficking of GABA(A)R, thus decaying miniature inhibitory postsynaptic current (mIPSC) of inhibitory synapses. In this study, using a pentylenetetrazol (PTZ)-induced epilepsy rat model, we found that Clptm1 regulates epileptic seizures by modulating GABA(A)R-mediated inhibitory synaptic transmission. First, we showed that Clptm1 expression was elevated in the PTZ-induced epileptic rats. Subsequently, we found that downregulation of Clptm1 expression protected against PTZ-induced seizures, which was attributed to an increase in the number of GABA(A)R gamma 2s in the plasma membrane and the amplitude of mIPSC. Taken together, our findings identify a new anti-seizure target that provides a theoretical basis for the development of novel strategies for the prevention and treatment of epilepsy."

基金机构："Epilepsy Research Fund of China Association Against Epilepsy (CAAE) [CW-2022-013]; National NaturalScience Fundation of China [81771390]; Open project of theClinical Medical Center of the First People'sHospital of Yunnan Province [2021LCZXXF-SJ02, 2022LCZXKF-SJ01]; Doctoral Research Fund of the FirstPeople's Hospital of Yunnan Province [KHBS-2022-014]"

基金资助正文："Epilepsy Research Fund of China Association Against Epilepsy (CAAE), Grant/AwardNumber: CW-2022-013; National NaturalScience Fundation of China, Grant/AwardNumber: 81771390; Open project of theClinical Medical Center of the First People'sHospital of Yunnan Province, Grant/AwardNumbers: 2021LCZXXF-SJ02, 2022LCZXKF-SJ01; Doctoral Research Fund of the FirstPeople's Hospital of Yunnan Province,Grant/Award Number: KHBS-2022-014"