机构:[1]Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing 400016, China内科系统神经内科(ICU)重庆医科大学附属第一医院[2]Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China内科科室神经内科昆明医科大学附属第一医院[3]Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, China
Repulsive guidance molecule a (RGMa) is a membrane-bound protein that inhibits axon outgrowth in the central nervous system. Temporal lobe epilepsy (TLE) is a common neurological disorder characterized by recurrent spontaneous seizures. To explore the role of RGMa in epilepsy, we investigated the expression of RGMa in patients with TLE, pilocarpine-induced rat model, and pentylenetetrazol kindling model of epilepsy, and then we performed behavioral, histological, and electrophysiological analysis by lentivirus-mediated overexpression of RGMa in the hippocampus of animal model. We found that RGMa was significantly decreased in TLE patients and in experimental rats from 6 h to 60 days after pilocarpine-induced seizures. In two types of epileptic animal models, pilocarpine-induced model and pentylenetetrazol kindling model, overexpression of RGMa in the hippocampus of rats exerted seizure-suppressant effects. The reduced spontaneous seizures were accompanied by attenuation of hippocampal mossy fiber sprouting. In addition, overexpression of RGMa inhibited hyperexcitability of hippocampal neurons via suppressing NMDAR-mediated currents in Mg2+-free-induced organotypic slice model. Collectively, these results demonstrate that overexpression of RGMa could be an alternative strategy for epilepsy therapy.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81071039]
第一作者机构:[1]Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing 400016, China[2]Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
共同第一作者:
通讯作者:
推荐引用方式(GB/T 7714):
Chen Ling,Gao Baobing,Fang Min,et al.Lentiviral Vector-Induced Overexpression of RGMa in the Hippocampus Suppresses Seizures and Mossy Fiber Sprouting[J].MOLECULAR NEUROBIOLOGY.2017,54(2):1379-1391.doi:10.1007/s12035-016-9744-2.
APA:
Chen, Ling,Gao, Baobing,Fang, Min,Li, Jie,Mi, Xiujuan...&Wang, Xuefeng.(2017).Lentiviral Vector-Induced Overexpression of RGMa in the Hippocampus Suppresses Seizures and Mossy Fiber Sprouting.MOLECULAR NEUROBIOLOGY,54,(2)
MLA:
Chen, Ling,et al."Lentiviral Vector-Induced Overexpression of RGMa in the Hippocampus Suppresses Seizures and Mossy Fiber Sprouting".MOLECULAR NEUROBIOLOGY 54..2(2017):1379-1391